MDA-9/Syntenin (SDCBP): Novel gene and therapeutic target for cancer metastasis. (May 2020)

• Record Type: Journal Article
• Authors: Das, Swadesh K.; Maji, Santanu; Wechman, Stephen L.; Bhoopathi, Praveen; Pradhan, Anjan K.; Talukdar, Sarmistha; Sarkar, Devanand; Landry, Joseph; Guo, Chunqing; Wang, Xiang-Yang; Cavenee, Webster K.; Emdad, Luni; Fisher, Paul B.
• Is Part Of: Pharmacological research. Volume 155(2020)
• Publication Date: 2020-05
• Subjects: AMD3100 (Compound CID: 65015) -- Dasatinib (Compound CID: 3062316) -- Docetaxel (Compound CID: 148124) -- Paclitaxel (Compound CID: 36314) -- Venetoclax (Compound CID: 49846579) -- Zoledronic acid (Compound CID: 68740); ADT androgen deprivation therapy -- ADP adenosine diphosphate -- ANGPTL4 angiopoietin-like 4 -- APP amyloid precursor protein -- CLEC-2 C-type lectin receptor 2 -- COX2 cyclooxygenase 2 -- DAMPs damage-associated molecular patterns -- DR6 death receptor 6 -- ECM extracellular matrix -- EGF epidermal growth factor -- EGFR epidermal growth factor receptor -- EMT epithelial mesenchymal transition -- FAK focal adhesion kinase -- FBDD fragment based drug discovery -- GBM glioblastoma multiforme -- GP glycoprotein -- GSCs glioblastoma stem cells -- HBEGF heparin-binding EGF-like growth factors -- IGF-1 insulin-like growth factor 1 -- IGF-1R insulin-like growth factor 1 receptor -- IGFBP-2 insulin-like growth factor binding protein-2 -- IL-5 interleukin-5 -- IL-8 interleukin-8 -- ITAM immune-receptor tyrosine-based activation motif -- LPA lysophosphatidic acid -- MDA-9 melanoma differentiation associated gene 9 -- MHC major histocompatibility complex -- MMPs matrix metalloproteinases -- NB neuroblastoma -- NFκB nuclear factor kappa-light-chain-enhancer of activated B cells -- NMR nuclear magnetic resonance -- PDGF platelet-derived growth factor -- PDZ post synaptic density protein (PSD95), drosophila disc large tumor suppressor (Dlg1), and zonula occludens-1 protein (zo-1) -- RANKL receptor activator of NF-κB ligand -- RKIP Raf kinase inhibitor protein -- S1P sphingosine 1-phosphate -- SDCBP syndecan binding protein -- SH3 Src homology 3 -- SH2 Src homology 2 -- SRE skeletal-related events -- STAT3 signal transducer and activator of transcription 3 -- TCGA the cancer genome atlas -- TEM trans-endothelial migration -- TF tissue factor -- TGF-α transforming growth factor alpha -- TGF-β transforming growth factor beta -- TGF-βR transforming growth factor beta receptor -- VCAM-1 vascular Cell Adhesion Molecule-1 -- VEGF vascular endothelial growth factor -- Zeb1 Zinc finger E-box-binding homeobox 1; MDA-9/Syntenin/SDCBP -- Cancer Metastasis -- Immunotherapy -- Glioblastoma multiforme -- Prostate adenocarcinoma -- Neuroblastoma; Pharmacology -- Periodicals; Pharmacology -- Periodicals; Research -- Periodicals; Médicaments -- Recherche -- Périodiques; Pharmacologie -- Périodiques; 615.105
• DOI: 10.1016/j.phrs.2020.104695
• Languages: English
• ISSNs: 1043-6618

Abstract

Abstract: The primary cause of cancer-related death from solid tumors is metastasis. While unraveling the mechanisms of this complicated process continues, our ability to effectively target and treat it to decrease patient morbidity and mortality remains disappointing. Early detection of metastatic lesions and approaches to treat metastases (both pharmacological and genetic) are of prime importance to obstruct this process clinically. Metastasis is complex involving both genetic and epigenetic changes in the constantly evolving tumor cell. Moreover, many discrete steps have been identified in metastatic spread, including invasion, intravasation, angiogenesis, attachment at a distant site (secondary seeding), extravasation and micrometastasis and tumor dormancy development. Here, we provide an overview of the metastatic process and highlight a unique pro-metastatic gene, melanoma differentiation associated gene-9/Syntenin (MDA-9/Syntenin) also called syndecan binding protein (SDCBP), which is a major contributor to the majority of independent metastatic events. MDA-9 expression is elevated in a wide range of carcinomas and other cancers, including melanoma, glioblastoma multiforme and neuroblastoma, suggesting that it may provide an appropriate target to intervene in metastasis. Pre-clinical studies confirm that inhibiting MDA-9 either genetically or pharmacologically profoundly suppresses metastasis. An additional benefit to blocking MDA-9 in metastatic cells is sensitization of these cells to a second therapeutic agent, which converts anti-invasion effects to tumor cytocidal effects. Continued mechanistic and therapeutic insights hold promise to advance development of truly effective therapies for metastasis in the future.