Abstract ES9-1: Role for IGF/Insulin signaling in breast cancer

Because insulin regulates glucose homeostasis, there has been extensive study into the molecular mechanisms of action of the insulin signaling system. Besides insulin, additional ligands, insulin-like growth factor (IGF) – I and –II and specific receptors for these ligands regulate cellular biology. The receptors share a similar structure and function. Once ligand binds the extracellular domain, a conformational change occurs allowing autophosphorylation of the intracellular tyrosine kinase domains and subsequent activation of multiple signaling pathways that ultimately result in cellular glucose uptake. Type 2 diabetes mellitus (T2D) results from deficient insulin receptor (InsR) signaling and subsequent elevation of serum glucose with compensatory attempt at regulating this pathophysiology by increased insulin production by the pancreas. While the etiology of T2D is complex and multi-factorial, obesity and insulin resistance are epidemiologically and mechanistically linked. Insulin was one of the first peptide growth factors known to stimulate breast cancer proliferation. Epidemiological data link obesity, metabolic syndrome (hyperinsulinemia), and elevated levels of IGFs to breast cancer risk and poor outcome for women diagnosed with breast cancer. These data, in part, led to the development of multiple targeted therapies for breast cancer. Receptor targeting of IGF-receptor signaling was not successful in hormone receptor (HR) positive breast cancers possibly because ...

Source: Cancer Research - February 18, 2016 Category: Cancer & Oncology Authors: Yee, D. Tags: Invited Speaker Abstracts Source Type: research