Syndecan-4 in Tumor Cell Motility.

Abstract

Simple SummaryCell migration is crucial fReaor metastasis formation and a hallmark of malignancy. The primary cause of high mortality among oncology patients is the ability of cancer cells to metastasize. To form metastasis, primary tumor cells must be intrinsically able to move. The transmembrane, heparan sulfate proteoglycan syndecan-4 (SDC4) exhibits multiple functions in signal transduction by regulating Rac1 GTPase activity and consequently actin remodeling, as well as regulating focal adhesion kinase, protein kinase C-alpha and the level of intracellular calcium. By affecting several signaling pathways and biological processes, SDC4 is involved in cell migration under physiological and pathological conditions as well. In this review, we discuss the SDC4-mediated cell migration focusing on the role of SDC4 in tumor cell movement.Syndecan-4 (SDC4) is a ubiquitously expressed, transmembrane proteoglycan bearing heparan sulfate chains. SDC4 is involved in numerous inside-out and outside-in signaling processes, such as binding and sequestration of growth factors and extracellular matrix components, regulation of the activity of the small GTPase Rac1, protein kinase C-alpha, the level of intracellular calcium, or the phosphorylation of focal adhesion kinase. The ability of this proteoglycan to link the extracellular matrix and actin cytoskeleton enables SDC4 to contribute to biological functions like cell adhesion and migration, cell proliferation, cytokinesis, cellular polarity, or mechanotransduction. The multiple roles of SDC4 in tumor pathogenesis and progression has already been demonstrated; therefore, the expression and signaling of SDC4 was investigated in several tumor types. SDC4 influences tumor progression by regulating cell proliferation as well as cell migration by affecting cell-matrix adhesion and several signaling pathways. Here, we summarize the general role of SDC4 in cell migration and tumor cell motility.