Abstract 4132: PTPRF negatively regulates c-MET signaling to inhibit cell migration in colon cancer

Abstract The spatiotemporal control of cell signaling requires a balancing act of protein kinases and phosphatases. Hyperactivation of signaling downstream of receptor tyrosine kinases (RTKs) is one of the most common mechanisms leading to oncogenic transformation in numerous cancer types. Although the activation process of RTKs has been extensively studied, the inactivation mechanisms mediated by tyrosine phosphatase are less understood. Previously, we have determined the molecular mechanisms by which protein tyrosine phosphatase receptor type F (PTPRF) regulates the Wnt pathway. In this study, we investigated the functional importance of PTPRF in controlling c-MET signaling in colon cancer. Downregulation of PTPRF in colon cancer cells using CRISPR-mediated gene deletion or shRNA-mediated gene silencing activates c-MET signaling at the level of GAB1 scaffolding protein upon HGF-induced receptor activation. Co-immunoprecipitation experiments indicate that PTPRF interacts with the c-MET receptor/GAB1 complex. In addition, PTPRF downregulation prolongs the phosphorylation of GAB1 in colon cancer cells treated with c-MET inhibitor. Functionally, PTPRF-loss markedly increases cell migration. Moreover, bioinformatics analysis of TCGA colon cancer patient data reveals that the expression of PTPRF gene is significantly decreased in tumor samples compared to normal controls. Taken together, these results identify PTPRF as a novel phosphatase of GAB1 that negatively regulates c-MET signaling. Decreased expression of PTPRF may play an important role in promoting tumor progression in colon cancer. Citation Format: Carolina Galeano-Naranjo, Haley Stanczyk, Warren Van Nort, Tianyan Gao. PTPRF negatively regulates c-MET signaling to inhibit cell migration in colon cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 4132.