Abstract 4291: p85α alters Gab2 phosphorylation profile in ovarian cancer

Abstract

Abstract Dysregulation of phosphatidylinositol 3-kinase (PI3K), which is essential for various cellular processes, is a common event in cancers. PIK3R1 encodes the PI3K class IA regulatory subunit p85α, which binds the p110 catalytic subunit forming heterodimeric PI3K complex. The PI3K associates with receptor tyrosine kinase, for example through the docking protein Gab2, to initiate downstream signaling events. Downregulation of p85α is frequently seen in cancers. However, the signaling changes driven by the downregulation remain to be elucidated. Our data herein indicate that reduced p85α expression leads to changes in the phosphorylation status of Gab2 at multiple amino acid residues. PIK3R1 siRNA decreased the levels of phosphorylated Y452 (a site implicated in binding p85α) and S210 (a site that may mediate negative feedback of Gab2 activity). Meanwhile, we observed an increase in phosphorylated S623, which was shown to involve in STAT activation. These findings provide mechanistic insights on the pathway activation upon downregulation of p85α in cancer. Citation Format: Xinran Li, Victor CY Mak, Annie NY Cheung, Gordon B. Mills, Lydia WT Cheung. p85α alters Gab2 phosphorylation profile in ovarian cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4291.