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

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:

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

Declaration of interest

The present study was supported in part by P01 CA104177 and R01 CA134721 given to Paul Fisher, R01 CA138540 given to Swadesh Das, R01 CA168517 to Maurizio Pellecchia and Paul Fisher; and a DoD grant W81XWH-10-PCRP-SIDA given to Paul Fisher and Wang Xiang-Yang. Paul Fisher and Swadesh Das were supported by the Samuel Waxman Cancer Research Foundation and Paul fisher was supported by the National Foundation for Cancer Research also. Wang Xiang-Yang and Swadesh Das are Harrison Scholars in the VCU Massey Cancer Center. Paul Fisher holds the Thelma Newmeyer Corman Chair in Cancer Research in the VCU Massey Cancer Center. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Notes

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