Ttp Inhibits Insulin Receptor Signals In Cancer Cell

Proceedings: AACR 106th Annual Meeting 2015; April 18-22, 2015; Philadelphia, PAInsulin receptors (IRs) belong to the large class of tyrosine kinase receptors and are activated by insulin, IGF-I, IGF-II and. The binding of ligands to the IR initiates a cascade of events leading to activation of signal transduction pathways, mainly PI3K and AKT pathways, and induce glucose uptake and cell proliferation. IR signaling pathway has been reported to be deregulated in cancer cells resulting in a range of clinical manifestations including cancer. It has been shown that the presence of IR was required for transformation induced by many oncogenes and over-expression or constitutive activation of IR gave rise to transformed phenotypes. Here, we report an unexpected role of a tumor suppressor tristetraprolin (TTP) in inhibiting IR. TTP bound to the AU-rich element (ARE) within the mRNA 3′UTRs of IR, enhanced the decay of their mRNAs and inhibited the metabolism of cancer cells. The ectopic expression of IR without their 3′UTRs blocked the inhibitory effects of TTP on the Warburg effect cancer. Our data propose a new model whereby the TTP down-regulates IR and plays an important role as a negative regulator of both the energy metabolism and proliferation of cancer cells.Citation Format: Ji Eun Yoon, VO MAI TRAM, Nal Ae Yoon, Jin Ho Back, Young Joo Min, Wha Ja Cho. TTP inhibits insulin receptor signals in cancer cell. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1170. doi:10.1158/1538-7445.AM2015-1170