Regulation of membrane-type 4 matrix metalloproteinase by SLUG contributes to hypoxia-mediated metastasis.

摘要: The hypoxic tumor environment has been shown to be critical cancer metastasis through the promotion of angiogenesis, induction epithelial-mesenchymal transition (EMT), and acquisition invasive potential. However, impact hypoxia on expression profile proteolytic enzymes involved in invasiveness is relatively unknown. Membrane-type 4 matrix metalloproteinase (MT4-MMP) a glycosyl-phosphatidyl inositol-anchored protease that overexpressed human cancers. detailed mechanisms regarding regulation function MT4-MMP cells remain Here, we demonstrate or overexpression hypoxia-inducible factor-1α (HIF-1α) induced cells. Activation SLUG, transcriptional factor regulating EMT process cancers, by HIF-1α was for under hypoxia. SLUG regulated transcription direct binding E-box located its proximal promoter. Short-interference RNA-mediated knockdown attenuated vitro vivo pulmonary colonization without affecting cell migratory ability. promoted modulation MMPs angiogenic factors. Finally, coexpression head neck predictive worse clinical outcome. These findings establish novel signaling pathway hypoxia-mediated elucidate underlying regulatory mechanism functional significance metastasis.