MDA-9/Syntenin/SDCBP: new insights into a unique multifunctional scaffold protein
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MDA-9/Syntenin/SDCBP: new insights into a unique multifunctional scaffold protein Anjan K. Pradhan 1 & Santanu Maji 1 & Swadesh K. Das 1,2,3 & Luni Emdad 1,2,3 & Devanand Sarkar 1,2,3 & Paul B. Fisher 1,2,3
# Springer Science+Business Media, LLC, part of Springer Nature 2020
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. Keywords mda-9 . Syntenin . PDZ domain . Metastasis . Cancer
1 Introduction Cancer represents a diverse collection of diseases in which transformed cells display uncontrolled proliferation and often invade nearby tissues (metastasis). Metastatic tumors can be distinguished from less aggressive and benign tumors, which do not spread and are curable [1]. The metastatic process involves the detachment of cancer cells from a primary tumor, invasion into the circulation and/or surrounding tissues, and establishment of micrometastases in distant tissues/organs [2]. In aggressive forms of cancer characterized by metastasis,
* Paul B. Fisher [email protected] 1
Department of Human and Molecular Genetics, Virginia Commonwealth University, School of Medicine, Richmond, VA 23298, USA
2
VCU Institute of Molecular Medicine, Virginia Commonwealth University, School of Medicine, Richmond, VA 23298, USA
3
VCU Massey Cancer Center, Virginia Commonwealth University, School of Medicine, Richmond, VA, USA
tumor cells must survive immune clearance and invade, proliferate, and establish new blood vessels (undergo angiogenesis) in distant sites [3]. There has been significant recent progress in deciphering the molecular underpinnings of cancer progression, resulting in enhanced therapies culminating in increased patient survival. Technological advances have led to enhanc
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