Fahri Saatcioglu

Representative Publications, Last 10 Years

1. ten Freyhaus, H., Calay, E.S., Yalcin, A., Vallerie, S.N., Yang, L., Calay, Z.Z., Saatcioglu, F., and Hotamisligil, G.S. (2012). Regulation of nicotinamide adenine dinucleotide phosphate-metabolism by STAMP2 is critical for macrophage inflammatory responses. Cell Metabolism16:81-89.
2. Jin, Y., Qu, S., Wang, L., Kristian, A., Maelandsmo, G.M., Jeronimo, C., Teixeira, M.R., Tekedereli, I., Sood, A., Lopez-Berestein, G., Ozpolat, B., Danielsen, H., and Saatcioglu, F. (2013). Kallikrein 4 integrates androgen and mTOR signalling in prostate cancer. Proc. Nat. Acad. Sci. USA, 110(28):E2572-81.
3. Jin, Y., Wang, L., Qu, S., Kristian, A., Mælandsmo, G.M., Yuca, E., Tekedereli, I., Gorgulu, K., Alpay, N., Sood, A., Lopez-Berestein, G., Fazli, L., Rennie, P., Risberg, B., Wæhre, H., Danielsen, H.D., Ozpolat, B., and Saatcioglu. F. (2015). STAMP2 increases oxidative stress and is critical for prostate cancer. EMBO Mol Med, 7(3):315-31
4. Sheng, X., Arnoldussen, Y.W., Storm, M., Tesikova, M., Jin, Y., Nenseth, H.Z., Sen Zhao, S., Mills, I.G., Fazli, L., Rennie, P., Risberg, B., Wæhre, H., Danielsen, H.E. Hotamisligil, G.S., and Saatcioglu, F. (2015). Divergent androgen regulation of unfolded protein response pathways drives prostate cancer. EMBO Mol Med, e201404509. 
6. Tesikova, M., Dezitter, X., Nenseth, H.Z., Klokk, T.I., Mueller, F., Hager, G.L., Saatcioglu, F. (2016). Divergent Binding and Transactivation by Two Related Steroid Receptors at the Same Response Element. J Biol Chem. pii: jbc.M115.684480. 
7. Sheng, X., Nenseth, H.Z., Qu, S., Fazli, L., Frahnow, T., Simon, L., Rennie, P., Danielsen, H., Theis, F.J., Patterson, J.B., Mills, I.G., Jin, Y., Saatcioglu, F. (2019). IRE1α-XBP1s pathway promotes prostate cancer by activating oncogenic signaling pathways. Nature Comm., Jan 24;10(1):323. doi: 10.1038/s41467-018-08152-3. 
8. Sikkeland, J., Lindstad, T., Dezitter, X., Qu, S., Nenseth, H. Z., Muhumed, R. M., Erikci-Ertunc, M., Gregor, M.F., and Saatcioglu, F. (2019). ER stress down-regulates Stamp2 expression in adipocytes by disruption of C/EBP promoter recruitment. Metabolism, Jan 30. pii: S0026-0495(19)30029-0. 
9. Pallmann, N., Livgard, M., Nenseth, H. Z., Xi, Y., Koc, D., Kahraman, N., Mokhlis, H.M., Ozpolat, B., Fazli, L., Rennie, P., Danielsen, H., Jin, Y., Saatcioglu, F. (2019). Regulation of the Integrated Stress Response through ATF4 and FAM129A is Critical for Prostate Cancer. Oncogene, Jul 16. doi: 10.1038/s41388-019-0879-2. 
10. Pallmann N, Deng, K., Livgard M, Tesikova, M., Nenseth, H.Z., Kahraman, N., Mokhlis, H.M., Ozpolat, B., Fazli, L., Rennie, P., Danielsen, H., Jin, Y., Kuzu, O.F., Saatcioglu, F. (2021). Stress mediated reprogramming of prostate cancer one-carbon cycle drives disease progression. Cancer Res., 81(15):4066-4078.
 

• Deng, Ke; Pällmann, Nora; Livgård, Marte; Kildal, Wanja; Pradhan, Manohar & Fazli, Ladan [Show all 10 contributors for this article] (2025). Endoplasmic reticulum stress-driven nucleotide catabolism fuels prostate cancer. Cancer Letters. ISSN 0304-3835. 630. doi: 10.1016/j.canlet.2025.217888. Full text in Research Archive Show summary

  Endoplasmic reticulum (ER) stress is a critical regulator of cancer cell metabolism and survival. In this study, we elucidate the coordinated roles of two key ER stress mediators, Activating Transcription Factor 4 (ATF4) and X-box Binding Protein 1 spliced (XBP1s), in regulating purine homeostasis in prostate cancer (PCa) cells. We demonstrate that ATF4 directly upregulates Molybdenum Cofactor Sulfurase (MOCOS), a key enzyme in purine catabolism, while XBP1s induces the expression of xanthine dehydrogenase (XDH), the principal MOCOS target in this pathway. Knockdown of MOCOS significantly impairs PCa cell proliferation as well as prostatosphere and colony formation in vitro, and inhibits tumor growth in preclinical mouse models of PCa. Mechanistically, MOCOS suppression leads to purine accumulation, disrupts pyrimidine synthesis, and causes nucleotide imbalance, resulting in replication fork stalling. This imbalance is also accompanied by a compromised glutathione-mediated antioxidant response, rendering the cells more susceptible to DNA damage. Importantly, targeting XDH, either genetically or biochemically, also significantly hinders PCa cell growth. Collectively, our data highlight the pivotal role of ER stress-mediated purine homeostasis in sustaining PCa cell growth.

• Kuzu, Omer; Granerud, Lars Jørgen Tvenge & Saatcioglu, Fahri (2025). Navigating the landscape of protein folding and proteostasis: from molecular chaperones to therapeutic innovations. Signal Transduction and Targeted Therapy. ISSN 2095-9907. 10(1). doi: 10.1038/s41392-025-02439-w. Full text in Research Archive Show summary

  Abstract Protein folding is a fundamental process ensuring that polypeptide chains acquire the correct three-dimensional structures required for biological function. This complex journey from nascent polypeptides to mature proteins is tightly regulated by the cellular proteostasis network—an integrated system of molecular chaperones, folding enzymes, and degradation machineries. Disruptions in this network lead to dysproteostasis, a pathological state implicated in a growing list of human diseases, including neurodegenerative disorders, metabolic syndromes, and cancer. In this review, we provide a comprehensive and multidimensional analysis of protein folding biology, tracing its evolution from early theoretical foundations to cutting-edge biophysical and computational techniques that now permit near-atomic-resolution modeling of folding dynamics. We explore the historical progression of protein folding research, including landmark discoveries of secondary structure, chaperone biology, and energy landscape theory. We detail the roles of key molecular chaperones across cytosolic, mitochondrial, and endoplasmic reticulum compartments, emphasizing their collaborative actions in protein folding and quality control. We also discuss the multifactorial causes of protein misfolding—from genetic mutations to aging and oxidative stress—and examine the pathological consequences, paying special attention to diseases characterized by toxic protein aggregation and loss of proteome fidelity. We then examine therapeutic innovations targeting proteostasis, including chaperone modulators, proteostasis pathway inhibitors, and emerging strategies to increase proteome resilience. By consolidating insights at the molecular, cellular, and systems levels, this review underscores the central role of protein folding homeostasis in health and disease and highlights novel opportunities for therapeutic intervention through the modulation of the proteostasis network.

• Ünal, Bilal & Saatcioglu, Fahri (2025). Targeting the unfolded protein response for cancer therapy: mitigating tumor adaptation and immune suppression. Biomarker Research. 13. doi: 10.1186/s40364-025-00813-y. Full text in Research Archive Show summary

  There are significant stress factors within the tumor microenvironment (TME), such as hypoxia, oxidative stress, and nutrient deprivation. These disrupt endoplasmic reticulum (ER) function in cancer cells, as well as the infiltrating immune cells, leading to activation of the unfolded protein response (UPR) signaling, which the tumor uses to mitigate stress and survive. There are three canonical UPR pathways that are regulated by respective ER-resident transmembrane sensors: inositol-requiring protein 1α (IRE1α), PKR-like ER kinase (PERK), and activating transcription factor 6 (ATF6); activation of these pathways results in expression of cognate transcription factors that regulate gene expression to mitigate ER stress. Persistent UPR activation in the TME has been linked to aberrant tumor growth, progression, metastasis, angiogenesis, and therapy resistance in different cancer types. In addition, modulation of UPR activity significantly impacts immune cell function at different levels further impacting its role on the TME. Therefore, there is now significant interest to design novel therapies that target the UPR to kill cancer cells and simultaneously enhance protective anti-tumor immunity. Here we summarize recent findings as to how targeting UPR signaling can induce tumor regression and at the same time galvanize the immune response. We discuss the potential of integrating UPR targeting with other therapies, such as immune checkpoint inhibition, highlighting emerging strategies to improve therapeutic efficacy and overcome resistance. These recent insights underscore the importance of UPR as a novel therapeutic target for cancer treatment.

• Hansen, Stian Bakke; Ünal, Bilal; Kuzu, Ömer Faruk & Saatcioglu, Fahri (2024). Immunological facets of prostate cancer and the potential of immune checkpoint inhibition in disease management. Theranostics. 14(18), p. 6913–6934. doi: 10.7150/thno.100555. Full text in Research Archive Show summary

  Prostate cancer (PCa) is the most common non-cutaneous cancer in men and a major cause of cancer-related deaths. Whereas localized PCa can be cured by surgery and radiotherapy, metastatic disease can be treated, but is not curable. Inhibition of androgen signaling remains the main therapeutic intervention for treatment of metastatic PCa, in addition to chemotherapy, radionuclide therapy and emerging targeted therapies. Although initial responses are favorable, resistance to these therapies invariably arise with development of castration resistant PCa (CRPC) and lethal phenotypes. Recent findings have implicated the crosstalk between PCa cells and the tumor microenvironment (TME) as a key factor for disease progression and metastasis, and the immune system is becoming an increasingly attractive target for therapy. Given the striking success of immune checkpoint inhibitors (ICIs) in various cancer types, preclinical and clinical studies have begun to explore their potential in PCa. It has become clear that the PCa TME is largely immunosuppressive, and ICI therapy does not have efficacy for PCa. Intense effort is therefore being made in the field to understand the mechanisms of suppression and to turn the immunosuppressive TME into an immune active one that would enable ICI efficacy. Herein we examine this recent body of knowledge and how the mutational landscape of PCa integrates with an immunosuppressive TME to circumvent ICI-mediated T-cell activity and tumor killing. We then review the emerging potential success of combinatorial ICI approaches, utility of careful patient selection, and potential novel strategies to improve the efficacy of ICI for PCa therapy.

• Saatcioglu, Fahri & Kuzu, Omer Faruk (2024). GeneSetR: A web server for gene set analysis based on genome-wide Perturb-Seq data. BioRxiv. ISSN 0362-4331. doi: 10.1101/2023.09.18.558211. Full text in Research Archive
• Korkmaz, Asli; Bernhardsen, Guro Pauck; Cirit, Burcu; Suzer, Gayem Koprucu; Kayan, Hale & Biçmen, Hülya [Show all 11 contributors for this article] (2024). Sudarshan Kriya Yoga Breathing and a Meditation Program for Burnout Among Physicians: A Randomized Clinical Trial. JAMA Network Open. 7(1). doi: 10.1001/jamanetworkopen.2023.53978. Full text in Research Archive Show summary

  Importance Physicians are exposed to high stress and strain that results in burnout, which affects them, their families, their patients, and the entire health care system; thus, there is an urgent need to develop methods to increase the resiliency of physicians. Sudarshan Kriya Yoga (SKY) is a comprehensive yoga breathing and meditation-based program that is a potential approach to mitigate physician burnout. Objective To determine whether SKY can reduce psychological distress and improve wellness in physicians. Design, Setting, and Participants This randomized clinical trial assessed the potential efficacy of SKY compared with a stress management education (SME) training as control. This study was conducted online from November 11, 2021, to March 14, 2022, and included physicians from Turkey, Germany, and Dubai. Both the SKY and the SME control groups received 1.5 hours of training for 3 consecutive days via a group video conference call. Participants were physicians willing to do some form of relaxation exercise everyday for 2 months. Exclusion criteria included presence of major illness and maintaining a regular mind-body program practice. Statistical analysis took place from March to November 2023. Interventions Participants were randomly assigned 1:1 into 2 groups—the SKY group or the SME (control) group—using a computer algorithm. After the 3-day instruction period, the participants in the SKY group practiced for approximately 30 minutes per day on their own and participated in a weekly 1-hour, group-based online follow-up practice. After the 3-day instruction period, participants in the SME group reviewed and applied the notes from stress management education training at their initiative and had a weekly 1-hour group-based online follow-up session. Main Outcomes and Measures The primary outcomes were stress and depression (measured by the 42-item Depression, Anxiety, and Stress Scale [DASS-42]) and insomnia measured by the Regensburg Insomnia Scale (RIS) with primary end point at 8 weeks. Secondary outcomes included anxiety (DASS-42); optimism (Life Orientation Test-Revised [LOT-R]); professional fulfillment, work exhaustion, interpersonal disengagement, and overall burnout (Professional Fulfillment Index [PFI]); and self-reported professional errors (Self-Reported Professional Error Questionnaire). Results This study included 129 participants (SME, 63 participants [48.9%]; SKY, 66 participants [51.1%]; 115 females [89.2%]; 14 males [10.8%]; mean [SD] age, 46.2 [9.0] years). Compared with the SME control group, participants in the SKY group had significantly decreased stress on the DASS-42 at posttraining (difference, −6.8 points; 95% CI, −9.6 to −4.1 points; P = .006) and at postintervention (difference, −6.0 points; 95% CI, −8.8 to −3.3 points; P = .03), significantly decreased depression at posttraining (difference, −5.7 points; 95% CI, −8.6 to −2.8 points; P < .001) and postintervention (difference, −5.4 points; 95% CI, −8.3 to −2.5 points; P < .001), and significantly decreased anxiety at postintervention. In addition, there was a significant decrease in insomnia from baseline to postintervention in the SKY group (difference, −0.3 points; 95% CI, −2.3 to 1.7 points; P = .01). The SKY group also showed significantly increased professional fulfillment as well as significant decreases in work exhaustion, interpersonal disengagement, and burnout. There was no effect on self-reported medical errors. Conclusions and Relevance In this randomized clinical trial, physicians who regularly practiced SKY throughout a 2-month period experienced improvements in wellness and decreased burnout. These data suggest that SKY may be an effective, practical, and safe strategy to increase wellness and mitigate burnout in physicians. Trial Registration ClinicalTrials.gov Identifier: NCT05956470

• Ünal, Bilal; Kuzu, Omer; Yang, Jin; Osorio, Daniel; Kildal, Wanja & Pradhan, Manohar [Show all 14 contributors for this article] (2024). Targeting IRE1α reprograms the tumor microenvironment and enhances anti-tumor immunity in prostate cancer. Nature Communications. 15(1), p. 1–21. doi: 10.1038/s41467-024-53039-1. Full text in Research Archive Show summary

  Unfolded protein response (UPR) is a central stress response pathway that is hijacked by tumor cells for their survival. Here, we find that IRE1α signaling, one of the canonical UPR arms, is increased in prostate cancer (PCa) patient tumors. Genetic or small molecule inhibition of IRE1α in syngeneic mouse PCa models and an orthotopic model decreases tumor growth. IRE1α ablation in cancer cells potentiates interferon responses and activates immune system related pathways in the tumor microenvironment (TME). Single-cell RNA-sequencing analysis reveals that targeting IRE1α in cancer cells reduces tumor-associated macrophage abundance. Consistently, the small molecule IRE1α inhibitor MKC8866, currently in clinical trials, reprograms the TME and enhances anti-PD-1 therapy. Our findings show that IRE1α signaling not only promotes cancer cell growth and survival but also interferes with anti-tumor immunity in the TME. Thus, targeting IRE1α can be a promising approach for improving anti-PD-1 immunotherapy in PCa.

• Saatcioglu, Fahri; Cirit, Burcu & Suzer, Gayem Koprucu (2022). The Promise of Well-Being Interventions to Mitigate Physician Burnout During the COVID-19 Pandemic and Beyond. JCO Oncology Practice (JCO OP). ISSN 2688-1527. 18(12), p. 808–814. doi: 10.1200/OP.22.00108. Full text in Research Archive Show summary

  The high degree of burnout in physicians, including oncologists, is detrimental to physicians themselves, their families, patients, health care organizations, and the health care systems as a whole. This dire situation has significantly worsened during the COVID-19 pandemic. It is well established that both organizational and individual measures are urgently needed to mitigate the negative consequences of physician burnout. Here, we review the research that has begun to indicate potential evidence-based individual approaches to promote physician well-being. We give an overview of these emerging programs and their importance, provide an example from our own experience, and enumerate considerations for future research. We also discuss the need for developing new approaches that are evidence-based and the best ways in which they can be incorporated in the health care setting. When judiciously combined with organizational approaches, preferentially as an integral part of them, individual wellness programs for physicians are poised to contribute significantly toward the much needed relief from physician burnout.

• Sikkeland, Jørgen; Ng, Matthew; Nenseth, Hatice Zeynep; Ünal, Bilal; Qu, Su & Jin, Yang [Show all 8 contributors for this article] (2022). STAMP2 suppresses autophagy in prostate cancer cells by modulating the integrated stress response pathway. American Journal of Cancer Research. 12(1), p. 327–336. Full text in Research Archive Show summary

  Six Transmembrane Protein of Prostate 2 (STAMP2) is critical for prostate cancer (PCa) growth. We previously showed that STAMP2 regulates the expression of stress induced transcription factor ATF4, which is implicated in starvation-induced autophagy. We therefore investigated whether STAMP2 is involved in the regulation of autophagy in PCa cells. Here we show that STAMP2 suppresses autophagy in PCa cells through modulation of the integrated stress response axis. We also find that STAMP2 regulates mitochondrial respiration. These findings suggest that STAMP2 has significant metabolic effects through mitochondrial function and autophagy, both of which support PCa growth.

• Jin, Yixin; Lorvik, Kristina Berg; Jin, Yang; Beck, Carole; Sike, Adam & Persiconi, Irene [Show all 10 contributors for this article] (2022). Development of STEAP1 targeting chimeric antigen receptor for adoptive cell therapy against cancer. Molecular Therapy Oncolytics. 26, p. 189–206. doi: 10.1016/j.omto.2022.06.007. Full text in Research Archive
• Nenseth, Hatice Zeynep; Sahu, Aparna; Saatcioglu, Fahri & Osguthorpe, Steven (2021). A Nutraceutical Formula Is Effective in Raising the Circulating Vitamin and Mineral Levels in Healthy Subjects: A Randomized Trial. Frontiers in Nutrition. 8. doi: 10.3389/fnut.2021.703394. Full text in Research Archive Show summary

  Low levels of nutrient intake are common in industrialized countries. This has negative implications on health and is associated with chronic diseases. Supplementation of vitamins, minerals, and key nutrients to optimal levels may, therefore, be beneficial for individual health and for the health economy. Although the use of supplements has become very common, due to a lack of monitoring, there is very limited data on the efficacy of supplementation with different formulas. In this study, we present the results of a randomized controlled study on the efficacy of a novel formulated nutraceutical, N247, in 250 healthy volunteers aged 26–75 years and a placebo control group (n = 35). The broad-spectrum formulation of N247 includes essential vitamins, minerals, and trace elements that are adequately balanced in regard to synergies and related metabolic functions. Moreover, tolerance, safety, and nutrient availability is an important aspect of daily, long-term use of N247. After 3 months of regular N247 use, levels of vitamins and minerals in serum were significantly increased in the N247 group compared with the control group and a placebo group, with excellent compliance rates. Coupled with additional natural ingredients that aim to increase the potency of the nutrients, N247 may represent a novel and beneficial supplement for individuals with nutritional deficiencies.

• Pihlstrøm, Nicklas; Jin, Yang; Nenseth, Hatice Zeynep; Kuzu, Omer Faruk & Saatcioglu, Fahri (2021). Stamp2 expression mediated by cytokines attenuates their growth-limiting effects in prostate cancer cells. Cancers. 13(7). doi: 10.3390/cancers13071579. Full text in Research Archive Show summary

  Inflammatory events and dysregulated cytokine expression are implicated in prostate cancer (PCa), but the underlying molecular mechanisms are poorly understood at present. We have previously identified six transmembrane protein of the prostate 2 (STAMP2, also known as STEAP4) as an androgen-regulated gene, as well as a key regulator of PCa growth and survival. STAMP2 is also regulated by, and participates in, inflammatory signaling in other tissues and pathologies. Here, we show that the proinflammatory cytokines interleukin 6 (IL-6) and Interleukin 1 beta (IL-1β) significantly increase and strongly synergize in promoting STAMP2 expression in PCa cells. The two cytokines increase androgen-induced STAMP2 expression, but not expression of other known androgen target genes, suggesting a unique interplay of androgens and cytokines in regulating STAMP2 expression. Interestingly, STAMP2 knockdown significantly increased the ability of IL-6 and IL-1β to inhibit PCa cell growth in vitro. These results suggest that STAMP2 may represent a unique node through which inflammatory events mediate their effects on PCa growth and survival.

• Pällmann, Nora; Ke, Deng; Livgård, Marte; Tesikova, Martina; Jin, Yixin & Frengen, Nicolai Sebastian [Show all 18 contributors for this article] (2021). Stress-mediated reprogramming of prostate cancer one-carbon cycle drives disease progression. Cancer Research. ISSN 0008-5472. 81(15), p. 4066–4078. doi: 10.1158/0008-5472.CAN-20-3956. Full text in Research Archive Show summary

  One-carbon (1C) metabolism has a key role in metabolic programming with both mitochondrial (m1C) and cytoplasmic (c1C) components. Here we show that activating transcription factor 4 (ATF4) exclusively activates gene expression involved in m1C, but not the c1C cycle in prostate cancer cells. This includes activation of methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) expression, the central player in the m1C cycle. Consistent with the key role of m1C cycle in prostate cancer, MTHFD2 knockdown inhibited prostate cancer cell growth, prostatosphere formation, and growth of patient-derived xenograft organoids. In addition, therapeutic silencing of MTHFD2 by systemically administered nanoliposomal siRNA profoundly inhibited tumor growth in preclinical prostate cancer mouse models. Consistently, MTHFD2 expression is significantly increased in human prostate cancer, and a gene expression signature based on the m1C cycle has significant prognostic value. Furthermore, MTHFD2 expression is coordinately regulated by ATF4 and the oncoprotein c-MYC, which has been implicated in prostate cancer. These data suggest that the m1C cycle is essential for prostate cancer progression and may serve as a novel biomarker and therapeutic target. Significance: These findings demonstrate that the mitochondrial, but not cytoplasmic, one-carbon cycle has a key role in prostate cancer cell growth and survival and may serve as a biomarker and/or therapeutic target.

• Guldvik, Ingrid Jenny; Zuber, Verena; Braadland, Peder Rustøen; Grytli, Helene Hartvedt; Ramberg, Håkon Andre & Lilleby, Wolfgang [Show all 18 contributors for this article] (2020). Identification and Validation of Leucine-rich alpha-2-glycoprotein 1 as a Noninvasive Biomarker for Improved Precision in Prostate Cancer Risk Stratification. European Urology Open Science. ISSN 2666-1691. 21, p. 51–61. doi: 10.1016/j.euros.2020.08.007. Full text in Research Archive Show summary

  Background More accurate risk assessments are needed to improve prostate cancer management. Objective To identify blood-based protein biomarkers that provided prognostic information for risk stratification. Design, setting, and participants Mass spectrometry was used to identify biomarker candidates from blood, and validation studies were performed in four independent cohorts retrospectively collected between 1988 and 2015. Outcome measurements and statistical analysis The primary outcome objectives were progression-free survival, prostate cancer–specific survival (PCSS), and overall survival. Statistical analyses to assess survival and model performance were performed. Results and limitation Serum leucine-rich α-2-glycoprotein 1 (LRG1) was found to be elevated in fatal prostate cancer. LRG1 provided prognostic information independent of metastasis and increased the accuracy in predicting PCSS, particularly in the first 3 yr. A high LRG1 level is associated with an average of two-fold higher risk of disease-progression and mortality in both high-risk and metastatic patients. However, our study design, with a retrospective analysis of samples spanning several decades back, limits the assessment of the clinical utility of LRG1 in today’s clinical practice. Thus, independent prospective studies are needed to establish LRG1 as a clinically useful biomarker for patient management. Conclusions High blood levels of LRG1 are unfavourable in newly diagnosed high-risk and metastatic prostate cancer, and LRG1 increased the accuracy of risk stratification of prostate cancer patients. Patient summary High blood levels of leucine-rich α-2-glycoprotein 1 are unfavourable in newly diagnosed high-risk and metastatic prostate cancer.

• Jin, Yang & Saatcioglu, Fahri (2020). Targeting the unfolded protein response in hormone-regulated cancers. Trends in Cancer. ISSN 2405-8033. 6(2), p. 160–171. doi: 10.1016/j.trecan.2019.12.001. Full text in Research Archive
• Pällmann, Nora; Livgård, Marte; Tesikova, Martina; Nenseth, Hatice Zeynep; Akkus, Erman & Sikkeland, Jørgen [Show all 20 contributors for this article] (2019). Regulation of the unfolded protein response through ATF4 and FAM129A in prostate cancer. Oncogene. ISSN 0950-9232. 38, p. 6301–6318. doi: 10.1038/s41388-019-0879-2. Full text in Research Archive Show summary

  Cancer cells exploit many of the cellular adaptive responses to support their survival needs. One such critical pathway in eukaryotic cells is the unfolded protein response (UPR) that is important in normal physiology as well as disease states, including cancer. Since UPR can serve as a lever between survival and death, regulated control of its activity is critical for tumor formation and growth although the underlying mechanisms are poorly understood. Here we show that one of the main transcriptional effectors of UPR, activating transcription factor 4 (ATF4), is essential for prostate cancer (PCa) growth and survival. Using systemic unbiased gene expression and proteomic analyses, we identified a novel direct ATF4 target gene, family with sequence similarity 129 member A (FAM129A), which is critical in mediating ATF4 effects on prostate tumorigenesis. Interestingly, FAM129A regulated both PERK and eIF2α in a feedback loop that differentially channeled the UPR output. ATF4 and FAM129A protein expression is increased in patient PCa samples compared with benign prostate. Importantly, in vivo therapeutic silencing of ATF4-FAM129A axis profoundly inhibited tumor growth in a preclinical PCa model. These data support that one of the canonical UPR branches, through ATF4 and its target gene FAM129A, is required for PCa growth and thus may serve as a novel therapeutic target.

• Sikkeland, Jørgen; Lindstad, Torstein; Nenseth, Hatice Zeynep; Dezitter, Xavier Gabriel M; Qu, Su & Muhumed, Ridhwan Mohamed [Show all 9 contributors for this article] (2019). Inflammation and ER stress differentially regulate STAMP2 expression and localization in adipocytes. Metabolism: Clinical and Experimental. ISSN 0026-0495. 93, p. 75–85. doi: 10.1016/j.metabol.2019.01.014. Full text in Research Archive Show summary

  Background Chronic ER stress and dysfunction is a hallmark of obesity and a critical contributor to metaflammation, abnormal hormone action and altered substrate metabolism in metabolic tissues, such as liver and adipocytes. Lack of STAMP2 in lean mice induces inflammation and insulin resistance on a regular diet, and it is dysregulated in the adipose tissue of obese mice and humans. We hypothesized that the regulation of STAMP2 is disrupted by ER stress. Methods 3T3-L1 and MEF adipocytes were treated with ER stress inducers thapsigargin and tunicamycin, and inflammation inducer TNFα. The treatments effect on STAMP2 expression and enzymatic function was assessed. In addition, 3T3-L1 adipocytes and HEK cells were utilized for Stamp2 promoter activity investigation performed with luciferase and ChIP assays. Results ER stress significantly reduced both STAMP2 mRNA and protein expression in cultured adipocytes whereas TNFα had the opposite effect. Concomitant with loss of STAMP2 expression during ER stress, intracellular localization of STAMP2 was altered and total iron reductase activity was reduced. Stamp2 promoter analysis by reporter assays and chromatin immunoprecipitation, showed that induction of ER stress disrupts C/EBPα-mediated STAMP2 expression. Conclusion These data suggest a clear link between ER stress and quantitative and functional STAMP2-deficiency.

• Sheng, Xia; Nenseth, Hatice Zeynep; Qu, Su; Kuzu, Ömer Faruk; Frahnow, Turid & Simon, Lukas [Show all 16 contributors for this article] (2019). IRE1α-XBP1s pathway promotes prostate cancer by activating c-MYC signaling. Nature Communications. 10:323, p. 1–12. doi: 10.1038/s41467-018-08152-3. Full text in Research Archive Show summary

  Activation of endoplasmic reticulum (ER) stress/the unfolded protein response (UPR) has been linked to cancer, but the molecular mechanisms are poorly understood and there is a paucity of reagents to translate this for cancer therapy. Here, we report that an IRE1α RNase-specific inhibitor, MKC8866, strongly inhibits prostate cancer (PCa) tumor growth as monotherapy in multiple preclinical models in mice and shows synergistic antitumor effects with current PCa drugs. Interestingly, global transcriptomic analysis reveal that IRE1α-XBP1s pathway activity is required for c-MYC signaling, one of the most highly activated oncogenic pathways in PCa. XBP1s is necessary for optimal c-MYC mRNA and protein expression, establishing, for the first time, a direct link between UPR and oncogene activation. In addition, an XBP1-specific gene expression signature is strongly associated with PCa prognosis. Our data establish IRE1α-XBP1s signaling as a central pathway in PCa and indicate that its targeting may offer novel treatment strategies.

• Winje, Ivan; Sheng, Xia; Hansson, Kenth-Arne; Solbrå, Andreas Våvang; Tennøe, Simen & Saatcioglu, Fahri [Show all 8 contributors for this article] (2018). Cachexia does not induce loss of myonuclei or muscle fibres during xenografted prostate cancer in mice. Acta Physiologica. ISSN 1748-1708. p. 1–9. doi: 10.1111/apha.13204. Full text in Research Archive
• Urbanucci, Alfonso; Barfeld, Stefan Jörg; Kytölä, Ville; Itkonen, Harri; Coleman, Ilsa M. & Vodák, Daniel [Show all 34 contributors for this article] (2017). Androgen receptor deregulation drives bromodomain-mediated chromatin alterations in prostate cancer. Cell reports. 19(10), p. 2045–2059. doi: 10.1016/j.celrep.2017.05.049. Full text in Research Archive Show summary

  Global changes in chromatin accessibility may drive cancer progression by reprogramming transcription factor (TF) binding. In addition, histone acetylation readers such as bromodomain-containing protein 4 (BRD4) have been shown to associate with these TFs and contribute to aggressive cancers including prostate cancer (PC). Here, we show that chromatin accessibility defines castration-resistant prostate cancer (CRPC). We show that the deregulation of androgen receptor (AR) expression is a driver of chromatin relaxation and that AR/androgen-regulated bromodomain-containing proteins (BRDs) mediate this effect. We also report that BRDs are overexpressed in CRPCs and that ATAD2 and BRD2 have prognostic value. Finally, we developed gene stratification signature (BROMO-10) for bromodomain response and PC prognostication, to inform current and future trials with drugs targeting these processes. Our findings provide a compelling rational for combination therapy targeting bromodomains in selected patients in which BRD-mediated TF binding is enhanced or modified as cancer progresses.

• Jin, Yang; Nenseth, Hatice Zeynep & Saatcioglu, Fahri (2017). Role of PLZF as a tumor suppressor in prostate cancer. OncoTarget. 8(41), p. 71317–71324. doi: 10.18632/oncotarget.19813. Full text in Research Archive
• Sikkeland, Jørgen; Sheng, Xia; Jin, Yang & Saatcioglu, Fahri (2016). STAMPing at the crossroads of normal physiology and disease states. Molecular and Cellular Endocrinology. ISSN 0303-7207. 425, p. 26–36. doi: 10.1016/j.mce.2016.02.013. Full text in Research Archive
• Lindstad, Torstein; Qu, Su; Sikkeland, Jørgen; Jin, Yang; Kristian, Alexandr & Mælandsmo, Gunhild [Show all 8 contributors for this article] (2016). STAMP2 is required for human adipose-derived stem cell differentiation and adiposite-facilitated prostrate cancer grown in vivo. OncoTarget. 8(54), p. 91817–91827. doi: 10.18632/oncotarget.11131. Full text in Research Archive
• Tesikova, Martina; Dezitter, Xavier Gabriel M; Nenseth, Hatice Zeynep; Klokk, Tove Irene; Mueller, Florian & Hager, Gordon L. [Show all 7 contributors for this article] (2016). Divergent binding and transactivation by two related steroid receptors at the same response element. Journal of Biological Chemistry. ISSN 0021-9258. 291(22), p. 11899–11910. doi: 10.1074/jbc.M115.684480. Full text in Research Archive
• Storm, Margrethe Larsdatter; Sheng, Xia; Arnoldussen, Yke Jildouw & Saatcioglu, Fahri (2016). Prostate cancer and the unfolded protein response. OncoTarget. 7(33), p. 54051–54066. doi: 10.18632/oncotarget.9912. Full text in Research Archive Show summary

  The endoplasmic reticulum (ER) is an essential organelle that contributes to several key cellular functions, including lipogenesis, gluconeogenesis, calcium storage, and organelle biogenesis. The ER also serves as the major site for protein folding and trafficking, especially in specialized secretory cells. Accumulation of misfolded proteins and failure of ER adaptive capacity activates the unfolded protein response (UPR) which has been implicated in several chronic diseases, including cancer. A number of recent studies have implicated UPR in prostate cancer (PCa) and greatly expanded our understanding of this key stress signaling pathway and its regulation in PCa. Here we summarize these developments and discuss their potential therapeutic implications.

• Sheng, Xia; Arnoldussen, Yke Jildouw; Storm, Margrethe Larsdatter; Tesikova, Martina; Nenseth, Hatice Zeynep & Zhao, Sen [Show all 15 contributors for this article] (2015). Divergent androgen regulation of unfolded protein response pathways drives prostate cancer. EMBO Molecular Medicine. ISSN 1757-4676. 7(6), p. 788–801. doi: 10.15252/emmm.201404509. Full text in Research Archive Show summary

  The unfolded protein response (UPR) is a homeostatic mechanism to maintain endoplasmic reticulum (ER) function. The UPR is activated by various physiological conditions as well as in disease states, such as cancer. As androgens regulate secretion and development of the normal prostate and drive prostate cancer (PCa) growth, they may affect UPR pathways. Here, we show that the canonical UPR pathways are directly and divergently regulated by androgens in PCa cells, through the androgen receptor (AR), which is critical for PCa survival. AR bound to gene regulatory sites and activated the IRE1α branch, but simultaneously inhibited PERK signaling. Inhibition of the IRE1α arm profoundly reduced PCa cell growth in vitro as well as tumor formation in preclinical models of PCa in vivo. Consistently, AR and UPR gene expression were correlated in human PCa, and spliced XBP‐1 expression was significantly upregulated in cancer compared with normal prostate. These data establish a genetic switch orchestrated by AR that divergently regulates the UPR pathways and suggest that targeting IRE1α signaling may have therapeutic utility in PCa.

• Jin, Yang; Ling, Wang; Qu, Su; Sheng, Xia; Kristian, Alexandr & Mælandsmo, Gunhild [Show all 20 contributors for this article] (2015). STAMP2 increases oxidative stress and is critical for prostate cancer. EMBO Molecular Medicine. ISSN 1757-4676. 7(3), p. 315–331. doi: 10.15252/emmm.201404181. Full text in Research Archive Show summary

  The six transmembrane protein of prostate 2 (STAMP2) is an androgen‐regulated gene whose mRNA expression is increased in prostate cancer (PCa). Here, we show that STAMP2 protein expression is increased in human PCa compared with benign prostate that is also correlated with tumor grade and treatment response. We also show that STAMP2 significantly increased reactive oxygen species (ROS) in PCa cells through its iron reductase activity which also depleted NADPH levels. Knockdown of STAMP2 expression in PCa cells inhibited proliferation, colony formation, and anchorage‐independent growth, and significantly increased apoptosis. Furthermore, STAMP2 effects were, at least in part, mediated by activating transcription factor 4 (ATF4), whose expression is regulated by ROS. Consistent with in vitro findings, silencing STAMP2 significantly inhibited PCa xenograft growth in mice. Finally, therapeutic silencing of STAMP2 by systemically administered nanoliposomal siRNA profoundly inhibited tumor growth in two established preclinical PCa models in mice. These data suggest that STAMP2 is required for PCa progression and thus may serve as a novel therapeutic target.

• Ertunc, Meric Erikci; Sikkeland, Jørgen; Fenaroli, Federico; Griffiths, Gareth Wyn; Daniels, Melissa C. & Cao, Haiming [Show all 8 contributors for this article] (2015). Secretion of fatty acid binding protein aP2 from adipocytes through a nonclassical pathway in response to adipocyte lipase activity. Journal of Lipid Research. ISSN 0022-2275. 56(2), p. 423–434. doi: 10.1194/jlr.M055798. Full text in Research Archive
• Sikkeland, Jørgen; Jin, Yang & Saatcioglu, Fahri (2014). Methods to assess lipid accumulation in cancer cells. Methods in Enzymology. ISSN 0076-6879. 542, p. 407–423. doi: 10.1016/B978-0-12-416618-9.00021-2. Full text in Research Archive
• Nenseth, Hatice Zeynep; Dezitter, Xavier; Tesikova, Martina; Mueller, Florian; Klokk, Tove Irene & Hager, Gordon L. [Show all 7 contributors for this article] (2014). Distinctly different dynamics and kinetics of two steroid receptors at the same response elements in living cells. PLOS ONE. 9(8). doi: 10.1371/journal.pone.0105204. Full text in Research Archive Show summary

  Closely related transcription factors (TFs) can bind to the same response elements (REs) with similar affinities and activate transcription. However, it is unknown whether transcription is similarly orchestrated by different TFs bound at the same RE. Here we have compared the recovery half time (t1/2), binding site occupancy and the resulting temporal changes in transcription upon binding of two closely related steroid receptors, the androgen and glucocorticoid receptors (AR and GR), to their common hormone REs (HREs). We show that there are significant differences at all of these levels between AR and GR at the MMTV HRE when activated by their ligands. These data show that two TFs bound at the same RE can have significantly different modes of action that can affect their responses to environmental cues.

• Qu, Su; Olafsrud, Solveig Mjelstad; Meza-Zepeda, Leonardo Andrés & Saatcioglu, Fahri (2013). Rapid Gene Expression Changes in Peripheral Blood Lymphocytes upon Practice of a Comprehensive Yoga Program. PLOS ONE. 8(4). doi: 10.1371/journal.pone.0061910. Full text in Research Archive
• Saatcioglu, Fahri (2013). Regulation of gene expression by yoga, meditation and related practices: A review of recent studies. Asian Journal of Psychiatry. ISSN 1876-2018. 6(1), p. 74–77. doi: 10.1016/j.ajp.2012.10.002. Full text in Research Archive
• Jin, Yang; Qu, Su; Tesikova, Martina; Ling, Wang; Kristian, Alexandr & Mælandsmo, Gunhild [Show all 19 contributors for this article] (2013). Molecular circuit involving KLK4 integrates androgen and mTOR signaling in prostate cancer. Proceedings of the National Academy of Sciences of the United States of America (PNAS). ISSN 0027-8424. 110(28), p. E2572–E2581. doi: 10.1073/pnas.1304318110. Full text in Research Archive
• Sikkeland, Jørgen & Saatcioglu, Fahri (2013). Differential Expression and Function of Stamp Family Proteins in Adipocyte Differentiation. PLOS ONE. 8(7). doi: 10.1371/journal.pone.0068249. Full text in Research Archive Show summary

  Six transmembrane protein of prostate (Stamp) proteins play an important role in prostate cancer cell growth. Recently, we found that Stamp2 has a critical role in the integration of inflammatory and metabolic signals in adipose tissue where it is highly expressed and regulated by nutritional and metabolic cues. In this study, we show that all Stamp family members are differentially regulated during adipogenesis: whereas Stamp1 expression is significantly decreased upon differentiation, Stamp2 expression is increased. In contrast, Stamp3 expression is modestly changed in adipocytes compared to preadipocytes, and has a biphasic expression pattern during the course of differentiation. Suppression of Stamp1 or Stamp2 expression both led to inhibition of 3T3-L1 differentiation in concert with diminished expression of the key regulators of adipogenesis - CCAAT/enhancer binding protein alpha (C/ebpa) and peroxisome proliferator-activated receptor gamma (Ppar?). Upon Stamp1 knockdown, mitotic clonal expansion was also inhibited. In contrast, Stamp2 knockdown did not affect mitotic clonal expansion, but resulted in a marked decrease in superoxide production that is known to affect adipogenesis. These results suggest that Stamp1 and Stamp2 play critical roles in adipogenesis, but through different mechanisms. This is an open-access article distributed under the terms of the Creative Commons Attribution License.

• Kaarbø, Mari; Storm, Margrethe; Qu, Su; Wæhre, Haakon; Risberg, Bjørn Åke & Danielsen, Håvard Emil [Show all 7 contributors for this article] (2013). TCTP is an androgen-regulated gene implicated in prostate cancer. PLOS ONE. 8(7:e69398). doi: 10.1371/journal.pone.0069398. Full text in Research Archive Show summary

  TCTP has been implicated in a plethora of important cellular processes related to cell growth, cell cycle progression, malignant transformation and inhibition of apoptosis. In addition to these intracellular functions, TCTP has extracellular functions and plays an important role in immune cells. TCTP expression was previously shown to be deregulated in prostate cancer, but its function in prostate cancer cells is largely unknown. Here we show that TCTP expression is regulated by androgens in LNCaP prostate cancer cells in vitro as well as human prostate cancer xenografts in vivo. Knockdown of TCTP reduced colony formation and increased apoptosis in LNCaP cells, implicating it as an important factor for prostate cancer cell growth. Global gene expression profiling in TCTP knockdown LNCaP cells showed that several interferon regulated genes are regulated by TCTP, suggesting that it may have a role in regulating immune function in prostate cancer. In addition, recombinant TCTP treatment increased colony formation in LNCaP cells suggesting that secreted TCTP may function as a proliferative factor in prostate cancer. These results suggest that TCTP may have a role in prostate cancer development. Copyright: © 2013 Kaarbø et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License.

• Lazarevic, Bato; Hammarstrøm, Clara Louise; Yang, Jing; Ramberg, Håkon Andre; Diep, Lien My & Karlsen, Steinar [Show all 10 contributors for this article] (2012). The effects of short-term genistein intervention on prostate biomarker expression in patients with localised prostate cancer before radical prostatectomy. British Journal of Nutrition. ISSN 0007-1145. 108(12), p. 2138–2147. doi: 10.1017/S0007114512000384. Full text in Research Archive
• Freyhaus, Henrik ten; Calay, Ediz S; Yalcin, Abdullah; Vallerie, Sara N; Yang, Ling & Calay, Zerrin Z [Show all 8 contributors for this article] (2012). Stamp2 Controls Macrophage Inflammation through Nicotinamide Adenine Dinucleotide Phosphate Homeostasis and Protects against Atherosclerosis. Cell Metabolism. ISSN 1550-4131. 16(1), p. 81–89. doi: 10.1016/j.cmet.2012.05.009. Full text in Research Archive
• Varisli, Lokman; Gonen-Korkmaz, Ceren; Debelec-Butuner, Bilge; Erbaykent-Tepedelen, Burcu; Muhammed, Hamed Sayed & Bogurcu, Nuray [Show all 8 contributors for this article] (2011). Ubiquitously Expressed Hematological and Neurological Expressed 1 Downregulates Akt-Mediated GSK3 beta Signaling, and Its Knockdown Results in Deregulated G2/M Transition in Prostate Cells. DNA and Cell Biology. ISSN 1044-5498. 30(6), p. 419–429. doi: 10.1089/dna.2010.1128. Full text in Research Archive
• Lazarevic, Bato; Boezelijn, Gro; Diep, Lien My; Kvernrød, Kristin; Øgren, Hans Olov & Ramberg, Håkon Andre [Show all 16 contributors for this article] (2011). Efficacy and Safety of Short-Term Genistein Intervention in Patients with Localized Prostate Cancer Prior to Radical Prostatectomy: A Randomized, Placebo-Controlled, Double-Blind Phase 2 Clinical Trial. Nutrition and Cancer. ISSN 0163-5581. 63(6), p. 889–898. doi: 10.1080/01635581.2011.582221. Full text in Research Archive
• Kaarbø, Mari; Mikkelsen, Øyvind Løveseter; Malerød, Lene; Qu, Su; Lobert, Viola & Akgul, Gulcan [Show all 9 contributors for this article] (2010). PI3K-AKT-mTOR pathway is dominant over androgen receptor signaling in prostate cancer cells. Cellular Oncology. ISSN 1570-5870. 32(1-2), p. 11–27. doi: 10.3233/CLO-2009-0487. Full text in Research Archive
• Kaarbø, Mari; Mikkelsen, Øyvind Løveseter; Malerød, Lene; Qu, Su; Lobert, Viola & Akgul, Gulcan [Show all 9 contributors for this article] (2010). PI3K-AKT-mTOR pathway is dominant over androgen receptor signaling in prostate cancer cells. Analytical Cellular Pathology. ISSN 2210-7177. doi: 10.3233/CLO-2009-0487. Full text in Research Archive
• Lindstad, Torstein; Jin, Yang; Ling, Wang; Qu, Su & Saatcioglu, Fahri (2010). STAMPs at the Crossroads of Cancer and Nutrition. Nutrition and Cancer. ISSN 0163-5581. 62(7), p. 891–895. doi: 10.1080/01635581.2010.509836. Full text in Research Archive
• Ling, Wang; Jin, Yang; Arnoldussen, Yke Jildouw; Jonson, Ida; Qu, Su & Mælandsmo, Gunhild [Show all 11 contributors for this article] (2010). STAMP1 Is Both a Proliferative and an Antiapoptotic Factor in Prostate Cancer. Cancer Research. ISSN 0008-5472. 70(14), p. 5818–5828. doi: 10.1158/0008-5472.CAN-09-4697. Full text in Research Archive
• Arnoldussen, Yke Jildouw & Saatcioglu, Fahri (2009). Dual specificity phosphatases in prostate cancer. Molecular and Cellular Endocrinology. ISSN 0303-7207. 309(1-2), p. 1–7. doi: 10.1016/j.mce.2009.05.019. Full text in Research Archive
• Arnoldussen, Yke Jildouw; Lorenzo, Petra Isabel O.; Einarsen, Maria; Wæhre, Haakon; Risberg, Bjørn & Mælandsmo, Gunhild M [Show all 8 contributors for this article] (2008). The Mitogen-Activated Protein Kinase Phosphatase Vaccinia H1-Related Protein Inhibits Apoptosis in Prostate Cancer Cells and Is Overexpressed in Prostate Cancer. Cancer Research. ISSN 0008-5472. 68(22), p. 9255–9264. doi: 10.1158/0008-5472.CAN-08-1224. Full text in Research Archive
• Lorenzo, Petra Isabel O. & Saatcioglu, Fahri (2008). Inhibition of apoptosis in prostate cancer cells by androgens is mediated through downregulation of c-Jun N-terminal kinase activation. Neoplasia. ISSN 1522-8002. 10, p. 418–428. doi: 10.1593/neo.07985. Full text in Research Archive
• Fladeby, Cathrine; Nigam, Shailly; Gupta, Shailly N.; Barois, Nicolas; Lorenzo, Petri & Simpson, Jeremy C. [Show all 8 contributors for this article] (2008). Human PARM-1 is a novel mucin-like, androgen-regulated gene exhibiting proliferative effects in prostate cancer cells. International Journal of Cancer. ISSN 0020-7136. 122(6), p. 1229–1235. doi: 10.1002/ijc.23185. Full text in Research Archive
• Lazarevic, Bato; Karlsen, Steinar & Saatcioglu, Fahri (2008). Genistein differentially modulates androgen-responsive gene expression and activates JNK in LNCaP cells. Oncology Reports. ISSN 1021-335X. 19, p. 1231–1235. Full text in Research Archive
• Klokk, Tove Irene; Kurys, Piotr Jerzy; Elbi, C; Nagaich, AK; Hendarwanto, A & Slagsvold, Thomas [Show all 9 contributors for this article] (2007). Ligand-specific dynamics of the androgen receptor at its response element in living cells. Molecular and Cellular Biology. ISSN 0270-7306. 27. doi: 10.1128/MCB.01297-06. Full text in Research Archive
• Kaarbø, Mari; Klokk, Tove Irene & Saatcioglu, Fahri (2007). Androgen signaling and its interaction with other signaling pathways in prostate cancer. Bioessays. ISSN 0265-9247. 29, p. 1227–1238. doi: 10.1002/bies.20676. Full text in Research Archive
• kjellgren, a; bood, sa; Axelsson, K; Norlander, T & Saatcioglu, Fahri (2007). Wellness through a comprehensive Yogic breathing program - A controlled pilot trial. BMC Complementary and Alternative Medicine. 7(1), p. 43–43. Full text in Research Archive
• Wellen, KE; Fucho, R; Gregor, MF; Furuhashi, M; Morgan, C & Lindstad, Torstein [Show all 10 contributors for this article] (2007). Coordinated regulation of nutrient and inflammatory responses by STAMP2 is essential for metabolic homeostasis. Cell. ISSN 0092-8674. 129. doi: 10.1016/j.cell.2007.02.049. Full text in Research Archive
• Klokk, Tove Irene; Kilander, Anette; Xi, Zhijun; Wæhre, Haakon; Risberg, Bjørn & Danielsen, Håvard Emil [Show all 7 contributors for this article] (2007). Kallikrein 4 is a proliferative factor that is overexpressed in prostate cancer. Cancer Research. ISSN 0008-5472. 67, p. 5221–5230. doi: 10.1158/0008-5472.CAN-06-4728. Full text in Research Archive
• Irer, SV; Alper, GE; Sezer, ED; Duman, E; Saatcioglu, Fahri & Yilmaz, C (2007). The effect of l-deprenyl on tissue mRNA expressions of NOS isoforms and NO levels in an experimental diabetes mellitus model. Journal of Neural Transmission. ISSN 0300-9564. 114. doi: 10.1007/s00702-007-0693-9. Full text in Research Archive
• Davidson, B; Xi, Zhijun & Saatcioglu, Fahri (2007). Kallikrein 4 is expressed in malignant mesotheliorna-further evidence for the histogenetic link between mesothelial and epithelial cells. Diagnostic Cytopathology. ISSN 8755-1039. 35. doi: 10.1002/dc.20588. Full text in Research Archive
• Aslan, G; Irer, B; Tuna, B; Yorukoglu, K; Saatcioglu, Fahri & Celebi, I (2006). analysis of NKX3.1 expression in prostate cancer tissues and correlation with clinicopathologic features. Pathology, Research and Practice. ISSN 0344-0338. 202(2), p. 93–98. Full text in Research Archive
• Lind, Gruo Elisabeth; Skotheim, Rolf Inge; Fraga, Mario F; Abeler, Vera Maria; Henrique, Rui & Saatcioglu, Fahri [Show all 9 contributors for this article] (2005). The loss of NKX3.1 expression in testicular - and prostate - cancers is not caused by promoter hypermethylation. Molecular Cancer. 4(1), p. 8–8. doi: 10.1186/1476-4598-4-8. Full text in Research Archive Show summary

  Background Recent studies have demonstrated that the NKX3.1 protein is commonly down-regulated in testicular germ cell tumors (TGCTs) and prostate carcinomas. The homeobox gene NKX3.1 maps to chromosome band 8p21, which is a region frequently lost in prostate cancer, but not in TGCT. Mutations have not been reported in the NKX3.1 sequence, and the gene is hypothesized to be epigenetically inactivated. In the present study we examined the methylation status of the NKX3.1 promoter in relevant primary tumors and cell lines: primary TGCTs (n = 55), intratubular germ cell neoplasias (n = 7), germ cell tumor cell lines (n = 3), primary prostate adenocarcinomas (n = 20), and prostate cancer cell lines (n = 3) by methylation-specific PCR and bisulphite sequencing. Results and Conclusions Down-regulation of NKX3.1 expression was generally not caused by promoter hypermethylation, which was only found in one TGCT. However, other epigenetic mechanisms, such as modulation of chromatin structure or modifications of histones, may explain the lack of NKX3.1 expression, which is seen in most TGCTs and prostate cancer specimens.

• Fronsdal, K & Saatcioglu, Fahri (2005). Histone deacetylase inhibitors differentially mediate apoptosis in prostate cancer cells. The Prostate. ISSN 0270-4137. 62. Full text in Research Archive
• Korkmaz, Ceren; Korkmaz, Kemal; Kurys, Piotr Jerzy; Elbi, Cem; Ling, Wang & Klokk, Tove Irene [Show all 11 contributors for this article] (2005). Molecular cloning and characterization of STAMP2, an andogen-regulated six transmembrane protein that is overexpressed in prostate cancer. Oncogene. ISSN 0950-9232. 24(31), p. 4934–45. Full text in Research Archive
• Davidson, Ben; Xi, Zhijun; Klokk, Tove Irene; Tropé, Claes Gøran; Dorum, Anne & Scheistroen, M [Show all 7 contributors for this article] (2005). Kallikrein 4 expression is up-regulated in epithelial ovarian carcinoma cells in effusions. American Journal of Clinical Pathology. ISSN 0002-9173. 123(3), p. 360–368. Full text in Research Archive
• Frønsdal, Katrine & Saatcioglu, Fahri (2005). Histone deacetylase inhibitors differentially mediate apoptosis in prostate cancer cells. The Prostate. ISSN 0270-4137. 62(3), p. 299–306. Full text in Research Archive
• Frønsdal, K. & Saatcioglu, Fahri (2005). Histone deacetylase inhibitors differentially mediate apoptosis in prostate cancer cells. The Prostate. ISSN 0270-4137. 62(3), p. 299–306. Full text in Research Archive
• Xi, Zhijun; Klokk, Tove Irene; Korkmaz, Kemal; Kurys, Piotr Jerzy; Elbi, C & Risberg, Bjørn [Show all 9 contributors for this article] (2004). Kallikrein 4 is a predominantly nuclear protein and is overexpressed in prostate cancer. Cancer Research. ISSN 0008-5472. 64(7), p. 2365–2370. Full text in Research Archive
• Korkmaz, Ceren; Korkmaz, Kemal; Manola, Judith; Xi, Zhijun; Risberg, Bjørn & Danielsen, Håvard Emil [Show all 10 contributors for this article] (2004). Analysis of androgen regulated homeobox gene NKX3.1 during prostate carcinogenesis. Journal of Urology. ISSN 0022-5347. 172, p. 1134–1139. Full text in Research Archive
• Lorenzo, Petra Isabel O. & Saatcioglu, Fahri (2004). Potentiation of androgen receptor transcriptional activity by inhibition of histone deacetylation--rescue of transcriptionally compromised mutants. Journal of Endocrinology. ISSN 0022-0795. 182, p. 377–377. Full text in Research Archive
• Xi, Zhijun; Kærn, Janne; Davidson, Ben; Klokk, Tove Irene; Risberg, Bjørn & Tropé, Claes Gøran [Show all 7 contributors for this article] (2004). Kallikrein 4 is associated with paclitaxel resistance in ovarian cancer. Gynecologic Oncology. ISSN 0090-8258. 94, p. 80–85. doi: 10.1016/j.ygyno.2004.03.044. Full text in Research Archive
• Bratland, Åse; Ragnhildstveit, Erlend; Bjørnland, Kristin; Andersen, Kristin; Mælandsmo, Gunhild Mari & Fodstad, Øystein [Show all 8 contributors for this article] (2003). The metalloproteinase inhibitor TIMP-2 is down-regulated by androgens in LNCaP prostate carcinoma cells. Clinical and Experimental Metastasis. ISSN 0262-0898. 20(6), p. 541–547. Full text in Research Archive
• Skotheim, Rolf Inge; Korkmaz, Kemal; Klokk, Tove Irene; Abeler, Vera M; Korlmaz, CG & Nesland, Jahn M [Show all 9 contributors for this article] (2003). NKX3.1 expression is lost in testicular germ cell tumors. American Journal of Pathology. ISSN 0002-9440. 163(6), p. 2149–2154. Full text in Research Archive
• Thuestad, Gunnar; Berghagen, Hege; Ragnhildstveit, Erlend; Krogsrud, Kristin; Apriletti, James & Saatcioglu, Fahri (2002). Corepressor SMRT Functions as a Coactivator for Thyroid Hormone Receptor T3Ralpha from a Negative Hormone Response Element. Journal of Biological Chemistry. ISSN 0021-9258. 277(51), p. 49517–49522. Full text in Research Archive
• Yamamoto, Takeshi; Saatcioglu, Fahri & Matsuda, T. (2002). Cross-talk between bone morphogenic proteins and estrogen receptor signaling. Endocrinology. ISSN 0013-7227. 143(7), p. 2635–2642. Full text in Research Archive Show summary

  Bone morphogenic proteins (BMPs) play central roles in differentiation, development, and physiological tissue remodeling. Estrogens have key roles in a variety of biological events, such as the development and maintenance of numerous target tissues. Previous studies demonstrated that estrogens suppress BMP functions by repressing BMP gene expression. Here we present a novel mechanism for the inhibitory effect of estrogens on BMP function. BMP-2-induced activation of Sma and Mad (mothers against decapentaplegic)-related protein (Smad) activity and BMP-2-mediated gene expression were suppressed by 17beta-E2 in breast cancer cells and mesangial cells. E2-mediated inhibition of Smad activation was reversed by tamoxifen, an ER antagonist. We provide evidence that the inhibitory action of ER on Smad activity was due to direct physical interactions between Smads and ER, which represents a novel mechanism for the cross-talk between BMP and ER signaling pathways

• Berghagen, H.; Krogsrud, K.; Ragnhildstveit, Erlend; Thuestad, Gunnar; Aprilletti, J. & Saatcioglu, Fahri (2002). Corepressor SMRT Functions as a Coactivator for Thyroid Hormone Receptor T3Ralpha from a Negative Hormone Response Element. Journal of Biological Chemistry. ISSN 0021-9258. 277(51), p. 49517–49522. Full text in Research Archive Show summary

  Nuclear receptors are ligand-modulated transcription factors that transduce the presence of lipophilic ligands into changes in gene expression. Nuclear receptor activity is regulated by ligand-induced interactions with coactivator or corepressor molecules. From a positive hormone response element (pHRE) and in the absence of hormone, corepressors SMRT and N-CoR are bound to some nuclear receptors such as the thyroid hormone (T3Rs) and retinoic acid receptors and mediate inhibition of basal levels of transcription. Ligand binding results in dissociation of corepressors and association of coactivators, resulting in the reversal of inhibition and a net activation of transcription. However, the role of cofactors on the activity of nuclear receptors from negative HREs (nHREs) is poorly understood. Here we show that corepressor SMRT can act as a potent coactivator for T3Ralpha from a nHRE; N-CoR has a similar but significantly attenuated activity. Mutagenesis of residues in the hinge region of T3Ralpha that block binding of SMRT and N-CoR inhibits ligand-independent transcriptional activation by T3Ralpha from a nHRE. These mutations also abrogate SMRT-mediated increase in transcriptional activity by T3Ralpha at a nHRE without significantly affecting ligand-dependent activation at a pHRE. Partial protease digestion coupled to the mobility shift assay indicate differences in the conformation of T3Ralpha-SMRT complexes bound to a pHRE versus a nHRE. These results suggest that allosteric changes resulting from binding of T3Ralpha to different response elements, i.e. pHREs versus nHREs, dictate whether a cofactor will function as a coactivator or a corepressor. This, in turn, greatly expands the repertoire of mechanisms used in modulating transcription without the need for expression of new regulatory molecules.

• Korkmaz, Kemal; Elbi, C.; Korkmaz, Ceren; Loda, M.; Hager, G. & Saatcioglu, Fahri (2002). Molecular cloning and characterization of STAMP1, a highly prostate-specific six transmembrane protein that is overexpressed in prostate cancer. Journal of Biological Chemistry. ISSN 0021-9258. 277(39), p. 36689–36696. Full text in Research Archive Show summary

  We have identified a novel gene, six transmembrane protein of prostate 1 (STAMP1), which is largely specific to prostate for expression and is predicted to code for a 490-amino acid six transmembrane protein. Using a form of STAMP1 labeled with green fluorescent protein in quantitative time-lapse and immunofluorescence confocal microscopy, we show that STAMP1 is localized to the Golgi complex, predominantly to the trans-Golgi network, and to the plasma membrane. STAMP1 also localizes to vesicular tubular structures in the cytosol and colocalizes with the early endosome antigen 1 (EEA1), suggesting that it may be involved in the secretory/endocytic pathways. STAMP1 is highly expressed in the androgen-sensitive, androgen receptor-positive prostate cancer cell line LNCaP, but not in androgen receptor-negative prostate cancer cell lines PC-3 and DU145. Furthermore, STAMP1 expression is significantly lower in the androgen-dependent human prostate xenograft CWR22 compared with the relapsed derivative CWR22R, suggesting that its expression may be deregulated during prostate cancer progression. Consistent with this notion, in situ analysis of human prostate cancer specimens indicated that STAMP1 is expressed exclusively in the epithelial cells of the prostate and its expression is significantly increased in prostate tumors compared with normal glands. Taken together, these data suggest that STAMP1 may have an important role in the normal prostate cell as well as in prostate cancer progression.

• Engedal, Nikolai; Korkmaz, Ceren & Saatcioglu, Fahri (2002). C-Jun N-terminal kinase is required for phorbol ester- and thapsigargin-induced apoptosis in the androgen responsive prostate cancer cell line LNCaP. Oncogene. ISSN 0950-9232. 21(7), p. 1017–1027. Full text in Research Archive Show summary

  In early, androgen dependent stages of prostate cancer, androgen withdrawal, the major course of therapy in prostate cancer, leads to a rapid regression of the tumor as a result of apoptosis. However, prostate cancer invariably progresses to an androgen independent and apoptosis resistant stage for which no curative treatment is available. The molecular details of regression upon androgen withdrawal and progression to a resistant state are largely unknown. Here we show that c-Jun N-terminal Kinase (JNK) is activated strongly and in a sustained fashion by 12-O-tetradecanoylphorbol 13-acetate (TPA) and thapsigargin (TG), two agents which were previously shown to lead to apoptosis in the androgen responsive prostate cancer cell line LNCaP. The time course of JNK induction by both compounds correlated very well with the onset and progression of apoptosis in LNCaP cells. Inhibition of either ERK or p38 pathways did not affect TPA-induced cell death. In the androgen-independent prostate cancer cell lines DU-145 and PC-3, and in the cervical carcinoma cell line HeLaS3, TPA did not lead to apoptosis and there were no significant changes in JNK activity upon TPA treatment. The failure of TPA to induce JNK activity in PC-3, DU-145, and HelaS3 cells was not due to a general defect in JNK signaling since ultraviolet (UV) irradiation dramatically increased JNK activity in all four cell lines. Specific inhibition of JNK by expression of the JNK Inhibitory Protein (JIP) dramatically inhibited both TPA- and TG-induced apoptosis. Furthermore, apoptosis induced by both agents was completely blocked by ectopic expression of the baculovirus caspase-inhibitor P35. Surprisingly, ZVAD-fmk, a cell-permeable fluoromethylketone inhibitor of caspases, had no effect on TPA-induced apoptosis, whereas it completely inhibited TG-induced cell death; JNK activity was not affected in either case. This indicates that ZVAD-fmk does not inhibit some of the caspases involved in TPA-induced apoptosis, and that despite the common requirement of JNK activation, TPA- and TG-induced cell death are mechanistically different. Furthermore, it also suggests that JNK is either upstream or independent of caspases in LNCaP cells. Collectively, these results indicate that apoptosis in LNCaP cells requires a sustained increase in JNK activity and caspase activation; components of these signaling pathways may be defective in the androgen independent prostate cancer cell lines.

• Saatcioglu, Fahri & Engedal, Nikolai (2001). Ceramide-induced cell death in the prostate cancer cell line LNCaP has both necrotic and apoptotic features. The Prostate. ISSN 0270-4137. 46, p. 289–297. Full text in Research Archive
• Thompson, J.H.; Saatcioglu, Fahri; Jänne, O. A. & Palvimo, J. J. (2001). Discrupted Amino-and Carboxyl-terminal Interactions of the Androgen Receptor Are Linked to Androgen Insensitivity. Molecular Endocrinology. ISSN 0888-8809. 15, p. 923–935. Full text in Research Archive
• Engedal, Nikolai; Korkmaz, Ceren & Saatcioglu, Fahri (2001). c-Jun N-terminal kinase is required for the induction of apoptosis in prostate cancer cells. Oncogene. ISSN 0950-9232. In Press. Full text in Research Archive
• Korkmaz, Kemal; Korkmaz, Ceren; Ragnhildstveit, Erlend; Pretlow, T. G. & Saatcioglu, Fahri (2001). KLK4/KLK1/Prostase has a distinctly different gene structure compared with other members of the kallikrein family Alternative cDNA forms and regulation by multiple hormones. DNA and Cell Biology. ISSN 1044-5498. 20, p. 435–445. Full text in Research Archive
• Slagsvold, Tore; Kraus, I.; Frønsdal, K. & Saatcioglu, Fahri (2001). A novel transcriptional function of the androgen receptor through triggering of coactivators. Journal of Biological Chemistry. ISSN 0021-9258. 276, p. 31030–31036. Full text in Research Archive
• Matsuda, T.; Junicho, A.; Yamamoto, Takeshi; Kishi, H.; Korkmaz, Kemal & Saatcioglu, Fahri [Show all 8 contributors for this article] (2001). Coss-talk between IL-6 and androgen receptor signaling in prostate carcinoma cells. Biochemical and Biophysical Research Communications - BBRC. ISSN 0006-291X. 283, p. 179–187. Full text in Research Archive
• Matsuda, T.; Yamamoto, Takeshi; Muraguchi, A. & Saatcioglu, Fahri (2001). Cross-talk between transforming growth factor-b and estrogen receptor signaling through Smad3. Journal of Biological Chemistry. ISSN 0021-9258. 276, p. 42908–42914. Full text in Research Archive
• Saatcioglu, Fahri; Engedal, Nikolai & Frønsdal, K. (2000). Efficient methods for DNA-mediated gene transfer into prostate cancer cell line LNCaP. The Prostate. ISSN 0270-4137. p. 111–117. Full text in Research Archive
• Saatcioglu, Fahri; Korkmaz, Kemal; Korkmaz, Ceren; Ragnhildstveit, Erlend & Pretlow, T. G. (2000). Full-length cDNA sequence and genomic organization of human NKX3.1-Alternative forms and regulation by both androgens and estrogens. Gene. ISSN 0378-1119. p. 25–36. Full text in Research Archive
• Saatcioglu, Fahri; Slagsvold, Tore; Bentzen, Tore; Kraus, I. & Palvimo, J. J. (2000). Mutational analysis of the androgen receptor AF-2 core domain reveals functional and mechanistic differences of conserved residues compared with other nuclear receptors. Molecular Endocrinology. ISSN 0888-8809. p. 1603–1617. Full text in Research Archive
• Saatcioglu, Fahri; Korkmaz, Kemal; Korkmaz, Ceren; Ragnhildstveit, Erlend & Pretlow, T. G. (2000). An Efficient procedure to clone hormone responsive genes from a specific tissue. DNA and Cell Biology. ISSN 1044-5498. p. 499–506. Full text in Research Archive
• Saatcioglu, Fahri; Junicho, A.; Matsuda, T.; Yamamoto, Takeshi; Kishi, H. & Korkmaz, Kemal [Show all 8 contributors for this article] (2000). Protein inhibitor of activated STAT3 regulates androgen receptor signaling in prostate carcinoma cells. Biochemical and Biophysical Research Communications - BBRC. ISSN 0006-291X. p. 9–13. Full text in Research Archive
• Yamamoto, Takeshi; Matsuda, T.; Junicho, A.; Kishi, H.; Saatcioglu, Fahri & Muraguchi, A. (2000). Cross-talk between signal transducer and activator of transcription 3 and estrogen receptor signaling. FEBS Letters. ISSN 0014-5793. p. 143–148. Full text in Research Archive
• Saatcioglu, Fahri; Apriletti, J.; Thuestad, Gunnar & Kraus, I. (2000). The N-terminal domain of thyroid hormone receptor alpha is required for all of its biological activities. DNA and Cell Biology. ISSN 1044-5498. p. 389–399. Full text in Research Archive

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• Sheng, Xia; Nenseth, Hatice Zeynep; Qu, Su; Kuzu, Omer; Frahnow, Turid & Simon, Lukas [Show all 16 contributors for this article] (2024). Correction to: IRE1α-XBP1s pathway promotes prostate cancer by activating c-MYC signaling (Nature Communications, (2019), 10, 1, (323), 10.1038/s41467-018-08152-3). Nature Communications. 15(1). doi: 10.1038/s41467-024-50645-x. Full text in Research Archive
• Storm, Margrethe; Kaarbo, Mari; Qu, Su; Wæhre, Haakon; Risberg, Bjørn Åke & Danielsen, Håkon [Show all 7 contributors for this article] (2013). TCTP is Androgen-Regulated and Over-Expressed in Prostate Cancer. The FASEB Journal. ISSN 0892-6638. 27. Full text in Research Archive
• Tesikova, Martina; Dezitter, Xavier; Klokk, Tove Irene; Kirli, Zeynep; Hager, Gordon L. & Saatcioglu, Fahri (2011). Differential effects of histone deacetylase inhibitors on transcription factor dynamics and activity at the same response element. The FASEB Journal. ISSN 0892-6638. 25. Full text in Research Archive
• Lindstad, Torstein & Saatcioglu, Fahri (2007). Feit og frisk? [Internet]. Forskning.no. Full text in Research Archive
• Lindstad, Torstein & Saatcioglu, Fahri (2007). Mus mot fedme. [Journal]. Dagbladet. Full text in Research Archive Show summary

  Med hjelp av mus tror forskere at det i framtida kan bli mulig å hindre livsstilssykdommer assosiert med overvekt og fedme.

• Lorenzo, Petra Isabel O.; Arnoldussen, Yke Jildouw & Saatcioglu, Fahri (2007). Molecular mechanisms of apoptosis in prostate cancer. Critical reviews in oncogenesis. ISSN 0893-9675. 13(1), p. 1–38. Full text in Research Archive
• Lazarevic, B; Karlsen, Steinar; Kucuk, O & Saatcioglu, Fahri (2004). Genistein differentially regulates prostate-enriched protein expression in prostate cancer. Journal of Nutrition. ISSN 0022-3166. 134, p. 1258S–1258S. Full text in Research Archive
• Xi, Zhijun; Klokk, Tove Irene & Saatcioglu, Fahri (2004). Expression of kallikrein 4 in epithelial ovarian carcinoma at different sites - evidence of divergent clinical role for tumor and stromal cells. Abstr 128. Full text in Research Archive
• Saatcioglu, Fahri (2004). Kallikrein 4 is a secreted protein - Response. Cancer Research. ISSN 0008-5472. 64, p. 8482–8483. Full text in Research Archive
• Davidson, Ben; Xi, Zhijun; Klokk, Tove Irene; Trope, Claes Gøran; Dørum, Anne & Scheistrøen, Marit [Show all 7 contributors for this article] (2004). Expression of kallikrein 4 in epithelial ovarian carcinoma at different sites - evidence of divergent clinical role for tumor and stromal cells. Abstr. nr 128, s 451. Gynecologic Oncology. ISSN 0090-8258. 92(1), p. 393–511. Full text in Research Archive
• Lazarevic, B; Karlsen, Steinar; Kucuk, O & Saatcioglu, Fahri (2003). Genistein differentially regulates prostate enriched protein expression in prostate cancer cells. Full text in Research Archive
• Thuestad, Gunnar; Kraus, Irene; Apriletti, James & Saatcioglu, Fahri (2000). DNA and Cell Biology The N-Terminal Domain of Thyroid Hormone Receptor-α Is Required for Its Biological Activities. ?. 19(7), p. 389–399. Full text in Research Archive

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