Non-small cell lung cancer cell survival crucially depends on functional insulin receptors.

摘要: Insulin plays an important role as a growth factor and its contribution to tumor proliferation is intensely discussed. It acts via the cognate insulin receptor (IR) but can also activate IGF1 (IGF1R). Apart from increasing proliferation, might have additional effects in lung cancer. Therefore, we investigated action of IR knockdown (KD) three (NCI-H292, NCI-H226 NCI-H460) independent non-small cell cancer (NSCLC) lines. All lines studied were found express IR, albeit with marked differences ratio two variants IR-A IR-B. activated classical signaling pathway autophosphorylation Akt phosphorylation. Moreover, activation MAPK was observed H292 cells, accompanied by enhanced proliferation. Lentiviral shRNA KD caused strong decrease survival all lines, indicating that go beyond enhancing Unspecific ruled out employing further shRNAs different insulin-responsive cells (human pre-adipocytes) for comparison. Caspase assays demonstrated strongly induced apoptosis these providing physiological basis rapid loss. In search underlying mechanism, analyzed alterations gene expression profile response KD. A induction certain cytokines (e.g. IL20 tumour necrosis factor) became obvious it turned trigger NSCLC tested. This indicates novel suppression pro-apoptotic cytokines.