MDA-9/syntenin: a positive gatekeeper of melanoma metastasis.
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.
Department of Human and Molecular Genetics, Virginia Commonwealth University, School of Medicine, Richmond, VA 23298, USA.
Swadesh K
SK
Das
Sujit K
SK
Bhutia
Timothy P
TP
Kegelman
Leyla
L
Peachy
Regina A
RA
Oyesanya
Santanu
S
Dasgupta
Upneet K
UK
Sokhi
Belal
B
Azab
Rupesh
R
Dash
Bridget A
BA
Quinn
Keetae
K
Kim
Paola M
PM
Barral
Zhao-zhong
ZZ
Su
Habib
H
Boukerche
Devanand
D
Sarkar
Paul B
PB
Fisher
D004792:Enzyme Precursors / Q000378:metabolism; D051417:Focal Adhesion Kinase 1 / Q000737:chemistry / Q000378:metabolism; D018093:Gelatinases / Q000378:metabolism; D006801:Humans; D008545:Melanoma / Q000473:pathology / Q000503:physiopathology / Q000556:secondary*; D008954:Models, Biological; D046912:Multiprotein Complexes / Q000737:chemistry; D009420:Nervous System / Q000503:physiopathology; D054730:Protein Interaction Domains and Motifs; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000737:chemistry / Q000378:metabolism; D015398:Signal Transduction; D053667:Syndecans / Q000378:metabolism; D053676:Syntenins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D025521:Tumor Suppressor Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology
D004792:Enzyme Precursors; D046912:Multiprotein Complexes; C109621:SDCBP protein, human; D053667:Syndecans; D053676:Syntenins; D025521:Tumor Suppressor Proteins; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human; D016392:Proto-Oncogene Proteins pp60(c-src); D018093:Gelatinases; C069860:progelatinase