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mda-9/Syntenin: More than Just a Simple Adapter Protein When It Comes to Cancer Metastasis

¹ Department of Human and Molecular Genetics, VCU Institute of Molecular Medicine, Massey Cancer Center, Medical College of Virginia, Virginia Commonwealth University School of Medicine, Richmond, Virginia and ² EA 4174, University Lyon 1, Institut National de la Santé et de la Recherche Médicale, Lyon, France

Requests for reprints: Paul B. Fisher or Devanand Sarkar, Department of Human and Molecular Genetics, School of Medicine, Virginia Commonwealth University, Sanger Hall Building, Room 11-015, 1101 East Marshall Street, Richmond, VA 23298. Phone: 804-828-9632; Fax: 804-827-1124; E-mail: pbfisher{at}vcu.edu or dsarkar{at}vcu.edu.

Key Words: metastasis • NF-B

Cancer is a progressive disease that, in many instances, if untreated, can culminate in metastatic spread of primary tumor cells to distant sites in the body. Metastasis frequently confers virulence and therapy resistance to cancer cells, and defining the molecular events that control metastasis will be mandatory to develop rational, targeted therapies for effective intervention, prevention of recurrence, and the "holy grail" of engendering a cure. Adapter proteins are physiologically pertinent molecules that, through interactions with key regulatory proteins via specific conserved domains, control important cellular events. Melanoma differentiation associated gene-9 (mda-9), also known as syntenin, is a PDZ domain–containing adapter protein that is involved in organization of protein complexes in the plasma membranes, regulation of B-cell development, intracellular trafficking and cell-surface targeting, synaptic transmission, and axonal outgrowth. Recent studies now define a seminal role for mda-9/sytenin in cancer metastasis. The present review provides a current perspective of our understanding of this important aspect of mda-9/sytenin, suggesting that this gene and its encoded protein and interacting protein partners may provide viable targets for intervening in the final and invariably the most lethal stage of cancer progression, namely, cancer metastasis. [Cancer Res 2008;68(9):3087–93]

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