Ali Mehboob

Abstract

Abnormal tumor cell survival is a key factor in cancer recurrence and death. This survival, and the subsequent metastasis (the spread of cancer), is tightly linked to the F-actin cytoskeleton, a cellular structure regulated by Actin Binding Proteins (ABPs). Vasodilator-stimulated phosphoprotein (VASP) is a central ABP that controls cell shape and polarity. VASP's activity is governed by two key phosphorylation sites, 1) Ser157: Phosphorylated by cAMP-dependent pathways, and 2) Ser239: Phosphorylated by cGMPdependent pathways. VASP interacts with other key actin regulators, Profilin-1 and Cofilin-1, to manage actin polymerization and stabilization, which either facilitates or suppresses metastasis. Our group's collective research, spanning colon cancer, lung cancer, and choriocarcinoma, clarifies the previously unknown roles of these interactomes, revealing that the two VASP phosphorylation sites are associated with opposite metastatic outcomes, a) The expression and cellular distribution of the Profilin-1/VASP pS157 axis promotes metastasis, while b) The Cofilin-1/VASPpS239 axis suppresses metastasis. Docosahexaenoic acid (DHA), an omega-3 fatty acid, is known to limit cancer cell proliferation and adhesion, but the mechanisms by which it reduces metastatic phenotypes have been unclear. Our investigations demonstrated that DHA inhibited cancer cell migration and viability. Furthermore, DHA altered the expression and cellular distribution of the ABPs within the VASP pathways which may be associated with its anti-metastatic mode of action. These findings highlights DHA's therapeutic potential against cancerous growth and metastasis.