國家衛生研究院 NHRI:Item 3990099045/11003
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    题名: Osteopontin-integrin engagement induces HIF-1α-TCF12- mediated endothelial-mesenchymal transition to exacerbate colorectal cancer
    其它题名: Osteopontin-integrin engagement induces HIF-1alpha-TCF12- mediated endothelial-mesenchymal transition to exacerbate colorectal cancer
    作者: Fan, CS;Chen, WS;Chen, LL;Chen, CC;Hsu, YT;Chua, KV;Wang, HD;Huang, TS
    贡献者: National Institute of Cancer Research
    摘要: Osteopontin (OPN) is a multi-functional phospho-glycoprotein that can stimulate angiogenesis through acting on endothelial cells. As angiogenic sprouting involves endothelial-to-mesenchymal transition (EndoMT), we are intrigued to know whether OPN exerts an effect on EndoMT. Clinically, we indeed detected EndoMT-derived cells next to OPN-expressing cells in colorectal cancer tissues. Furthermore, we treated OPN to primary cultures of endothelial cells to investigate the EndoMT-inducing activity and the underlying mechanisms. Integrin αVβ3 rather than CD44 is involved in OPNinduced EndoMT. OPN-integrin αVβ3 engagement induces HIF-1α expression through a PI3K/Akt/TSC2-mediated and mTORC1-dependent protein synthesis pathway, which in turn trans-activates TCF12 gene expression. TCF12 further interacts with EZH2 and histone deacetylases to transcriptionally repress VE-cadherin gene and thus facilitates EndoMT. Like cancer-associated fibroblasts, EndoMT-derived cells promote tumor growth and metastasis by secreting certain proteins. Secreted HSP90α is a candidate suggested by microwestern array assay, and is herein verified to induce stemness properties in colorectal cancer cells. As OPN is overexpressed in human cancers, OPN-induced EndoMT and EndoMT-derived cells can be potentially taken as cancer therapeutic targets.
    日期: 2018-12-22
    關聯: Oncotarget. 2018 Dec 22;9(4):4998-5015.
    Link to: http://dx.doi.org/10.18632/oncotarget.23578
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000422651700058
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85040468088
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