[Frontiers in Bioscience 17, 1-15, January 1, 2012]
MDA-9/syntenin: a positive gatekeeper of melanoma metastasis
Swadesh K. Das1, Sujit K. Bhutia1, Timothy P. Kegelman1, Leyla Peachy1, Regina A. Oyesanya1, Santanu Dasgupta1, Upneet K. Sokhi1, Belal Azab1, Rupesh Dash1, Bridget A. Quinn1, Keetae Kim1, Paola M. Barral1, Zhao-zhong Su1, Habib Boukerche2, Devanand Sarkar1,3,4, Paul B. Fisher1,3,4
1Department of Human and Molecular Genetics, Virginia Commonwealth University, School of Medicine, Richmond, VA 23298, 2INSERM U583, Montpellier, France, 3VCU Institute of Molecular Medicine, Virginia Commonwealth University, School of Medicine, Richmond, VA 23298, 4VCU Massey Cancer Center, Virginia Commonwealth University, School of Medicine, Richmond, VA 23298
TABLE OF CONTENTS
Melanoma differentiation associated gene-9 (MDA-9), synonymous with syntenin, is an adapter protein that provides a central role in regulating cell-cell and cell-matrix adhesion. MDA-9/syntenin transduces signals from the cell-surface to the interior through its interaction with a plethora of additional proteins and actively participates in intracellular trafficking and cell-surface targeting, synaptic transmission, and axonal outgrowth. Recent studies demarcate a seminal role of MDA-9/syntenin in cancer metastasis. In the context of melanoma, MDA-9/syntenin functions as a positive regulator of melanoma progression and metastasis through interactions with c-Src and promotes the formation of an active FAK/c-Src signaling complex leading to NF-k B and matrix metalloproteinase (MMP) activation. The present review provides a current perspective of our understanding of the important features of MDA-9/syntenin and its significant role in tumor cell metastasis with special focus on molecular mechanism of action.