The MDA-9/Syntenin/IGF1R/STAT3 Axis Directs Prostate Cancer Invasion.

摘要: Although prostate cancer is clinically manageable during several stages of progression, survival severely compromised once cells invade and metastasize to distant organs. Comprehending the pathobiology invasion required for developing efficacious targeted therapies against metastasis. Based on bioinformatics data, we predicted an association melanoma differentiation-associated gene-9 [syntenin, or syndecan binding protein (SDCBP)] in progression. Using tissue samples from various Gleason stage patients with adjacent normal tissue, a series cell lines (with differing tumorigenic/metastatic properties), mda-9/syntenin-manipulated variants (including loss-of-function gain-of-function lines), CRISPR/Cas9 stable MDA-9/Syntenin knockout cells, now confirm relevance dependence MDA-9/syntenin invasion. physically interacted insulin-like growth factor-1 receptor following treatment factor protein-2 (IGFBP2), regulating downstream signaling processes that enabled STAT3 phosphorylation. This activation enhanced expression MMP2 MMP9, two established enzymes positively regulate In addition, MDA-9/syntenin-mediated upregulation proangiogenic factors including IGFBP2, IL6, IL8, VEGFA also facilitated migration cells. Collectively, our results draw attention as positive regulator metastasis, potential application targeting this molecule inhibit metastasis potentially other cancers.Significance: study provides new mechanistic insight into proinvasive role has therapeutic prevent Cancer Res; 78(11); 2852-63. ©2018 AACR.