Targeting tumor invasion: the roles of MDA-9/Syntenin

Expert Opin Ther Targets. 2015 Jan;19(1):97-112. doi: 10.1517/14728222.2014.959495. Epub 2014 Sep 15.

Abstract

Introduction: Melanoma differentiation-associated gene - 9 (MDA-9)/Syntenin has become an increasingly popular focus for investigation in numerous cancertypes. Originally implicated in melanoma metastasis, it has diverse cellular roles and is consistently identified as a regulator of tumor invasion and angiogenesis. As a potential target for inhibiting some of the most lethal aspects of cancer progression, further insight into the function of MDA-9/Syntenin is mandatory.

Areas covered: Recent literature and seminal articles were reviewed to summarize the latest collective understanding of MDA-9/Syntenin's role in normal and cancerous settings. Insights into its participation in developmental processes are included, as is the functional significance of the N- and C-terminals and PDZ domains of MDA-9/Syntenin. Current reports highlight the clinical significance of MDA-9/Syntenin expression level in a variety of cancers, often correlating directly with reduced patient survival. Also presented are assessments of roles of MDA-9/Syntenin in cancer progression as well as its functions as an intracellular adapter molecule.

Expert opinion: Multiple studies demonstrate the importance of MDA-9/Syntenin in tumor invasion and progression. Through the use of novel drug design approaches, this protein may provide a worthwhile therapeutic target. As many conventional therapies do not address, or even enhance, tumor invasion, an anti-invasive approach would be a worthwhile addition in cancer therapy.

Keywords: EGFR; PDZ; angiogenesis; breast cancer; c-Src; exosomes; glioblastoma; glioma; integrin; invasion; melanoma; melanoma differentiation-associated gene – 9; metastasis; small cell lung carcinoma; syndecan binding protein; syntenin; urothelial cell carcinoma; uveal melanoma.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Animals
  • Humans
  • Inflammation / metabolism
  • Neoplasm Invasiveness
  • Neoplasms / metabolism*
  • Neoplasms / pathology
  • Neovascularization, Pathologic / metabolism
  • Syntenins / metabolism*

Substances

  • SDCBP protein, human
  • Syntenins