Abstract 3449: AGL loss promotes anchorage independent growth of non-small cell lung cancer by activating FAK

Abstract

Abstract Loss of glycogen debranching enzyme (AGL) has been shown to promote growth of bladder and non-small cell lung cancer. AGL loss predominantly assists anchorage independent growth of non-small cell lung cancer (NSCLC) cells. However the mechanism driving this anchorage independent growth with AGL loss is not well understood. To identify the driver pathways which contributions to increased anchorage independent growth with AGL loss, we carried out a phospho-kinase screen in A549 NSCLC cells with and without AGL expression. The kinase screen identified an increase in phospho-FAK (Tyr 576/577) levels with loss of AGL. The result of the screen was validated using separate independent Western blot experiments in A549 and other NSCLC cell lines which showed an increase in FAK activation at Tyr 576/577 with loss of AGL. We next treated NSCLC cells with and without AGL with FAK specific inhibitor (FAK inhibitor 14). Treatment with FAK inhibitor 14 had a greater cytotoxic effect (p<0.05) on NSCLC cells that have AGL loss. These data suggest that activation of FAK is a major driver of anchorage independent growth in NSCLC cells that have lost AGL expression and inhibition of FAK activity can serve as a therapeutic avenue for NSCLC patients with low tumor AGL expression. Citation Format: Sunny Guin, Craig Richmond. AGL loss promotes anchorage independent growth of non-small cell lung cancer by activating FAK [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3449.