Abstract
Tumor metastasis comprises a series of coordinated events that culminate in dissemination of cancer cells to distant sites within the body representing the greatest challenge impeding effective therapy of cancer and the leading cause of cancer-associated morbidity. Cancer cells exploit multiple genes and pathways to colonize to distant organs. These pathways are integrated and regulated at different levels by cellular- and extracellular-associated factors. Defining the genes and pathways that govern metastasis can provide new targets for therapeutic intervention. Melanoma differentiation associated gene-9 (mda-9) (also known as Syntenin-1 and SDCBP (Syndecan binding protein)) was identified by subtraction hybridization as a novel gene displaying differential temporal expression during differentiation of melanoma. MDA-9/Syntenin is an established Syndecan binding protein that functions as an adaptor protein. Expression of MDA-9/Syntenin is elevated at an RNA and protein level in a wide-range of cancers including melanoma, glioblastoma, neuroblastoma, and prostate, breast and liver cancer. Expression is increased significantly in metastatic cancer cells as compared with non-metastatic cancer cells or normal cells, which make it an attractive target in treating cancer metastasis. In this review, we focus on the role and regulation of mda-9 in cancer progression and metastasis.
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Funding
We thank the members of the Fisher and Sarkar laboratories for their contributions to our understanding of MDA-9/Syntenin-1/SDCBP that serve as a basis for this review. The present studies were supported in part by NCI R01 CA244993 (DS and PBF), the National Foundation for Cancer Research (NFCR) (PBF), and a sponsored research agreement from InVaMet Therapeutics, Inc. (IVMT) (SKD). DS is the Harrison Foundation Distinguished Professor in Cancer Research. PBF holds the Thelma Newmeyer Corman Chair in Oncology.
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PBF is co-founder, CEO, and has an ownership interest in InVaMet Therapeutics, Inc. (IVMT). VCU and the Sanford Burnham Prebys Medical Discovery Institute also have an equity interest in IVMT. SD is recipient of a Sponsored Research Agreement between VCU and IVMT.
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Pradhan, A.K., Maji, S., Das, S.K. et al. MDA-9/Syntenin/SDCBP: new insights into a unique multifunctional scaffold protein. Cancer Metastasis Rev 39, 769–781 (2020). https://doi.org/10.1007/s10555-020-09886-7
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DOI: https://doi.org/10.1007/s10555-020-09886-7