BMB Section Seminar: Taxonomy of Prostate Cancer & Systemic Insulin Resistance
The molecular taxonomy of metastatic prostate cancer
Peter Nelson, Fred Hutchinson Cancer Research Center, Seattle, WA
Personalized medicine and precision oncology are dependent on two related concepts to achieve success. First, the molecular composition of cancers between individual patients must be different such that a therapy selected for one individual would be different than a treatment selected for a different individual, based on underlying biology. Second, tumor diversity within an individual must be limited, such that a selected treatment would target all or most tumor cells within an individual. This presentation will discuss current information capable of classifying subtypes of prostate cancer amenable to specific therapeutics and assess the extent of tumor heterogeneity in metastatic prostate cancer.
JNK in local and systemic insulin resistance
Carmen Caelles Franch, University of Barcelona, Spain
The c-Jun N-terminal kinase (JNK) inhibits insulin receptor (InR) signaling by targeting the InR substrate (IRS). In physiological conditions, JNK functions as a negative feedback regulator of the InR pathway however, when abnormally activated in insulin target tissues, JNK promotes insulin resistance. In fact, we have previously shown that JNK inhibition is required for the insulin sensitizing action of the thiazolidinedione family of drugs. In addition, JNK is involved in promoting the death of the pancreatic insulin producing cells (beta-cells). We have been studying the phenotype of a transgenic mice in which JNK is specifically activated in these pancreatic beta-cells, and shown that, in this context, JNK promotes glucose intolerance by interfering with the paracrine action of insulin.