Phosphatase regulation of cellular motility in the tumor microenvironment

Abstract

An increasing number of anti‐tumor therapies have focused on angiogenesis pathways. Targeting various aspects of angiogenesis has been shown to disrupt tumor growth and reduce tumor progression and recurrence. Our studies show that treatment of microvascular endothelial cells with tumor‐conditioned media, and TGF‐β specifically, leads to alterations in the activity of protein phosphatases PP1 and PP‐2A. We hypothesize that dephosphorylation of focal adhesion complex targets lead to an increase in TGF‐β –induced endothelial motility. Specifically, our studies have shown that paxillin, a crucial focal adhesion adapter protein is a novel PP1 binding partner. Paxillin phosphorylation has been shown to induce both focal adhesion stability and turnover, therefore site‐specific phosphatase activity is a key regulatory mechanism. Elucidation of mechanisms of phosphatase regulation and interaction in the tumor microenvironment will provide insight into mechanisms of angiogenesis and novel targets for therapeutics. This work is supported by Dept. of Veteran's Affairs and NIH funding.