Abstract 2403: Regulation of FAK phosphorylation by serine/threonine protein phosphatases in cancer cells

Abstract

Abstract Focal adhesion kinase (FAK), a non-receptor tyrosine kinase, is activated by growth factors and integrin clustering, promoting cell migration, a critical step for cancer metastasis. The activity of FAK is closely associated with the phosphorylation of diverse residues, which are mediated by various protein tyrosine kinases and phosphatases. Previous studies have demonstrated that serine/threonine protein phosphatase 5 (PP5) promotes cell migration, while protein phosphatase 2A (PP2A) inhibits cell migration. However, whether PP5 and PP2A regulate cell migration by mediating FAK phosphorylation is poorly understood. In this study, we found that overexpression of PP5 decreased FAK phosphorylation at S722, and knockdown of PP5 increased p-FAK (S722) in a spectrum of tumor cell lines. Our co-immunoprecipitation (co-IP) results showed an interaction between PP5 and FAK. In addition, we observed that overexpression of PP5 induced S178 phosphorylation of paxillin, an FAK interacting protein. However, there was no physical interaction between PP5 and paxillin, indicating an indirect regulation. In addition, knockdown of PP2A enhanced the phosphorylation of FAK and conferred resistance to rapamycin inhibition of IGF-I-stimulated phosphorylation of FAK. To our surprise, by co-IP, we failed to detect any direct interaction between FAK and PP2A. Further research will determine how PP5 and PP2A regulate cell migration through FAK and paxillin. Acknowledgements This work was supported by the Feist-Weiller Cancer Center (FWCC) Bridge Award (S.H.), Shreveport, LA, USA Citation Format: Lin Li, Lie Liu, Shile Huang. Regulation of FAK phosphorylation by serine/threonine protein phosphatases in cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2403.