國家衛生研究院 NHRI:Item 3990099045/9962
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    題名: Angiopoietin-like protein 1 antagonizes MET receptor activity to repress sorafenib resistance and cancer stemness in hepatocellular carcinoma
    作者: Chen, HA;Kuo, TC;Tseng, CF;Ma, JT;Yang, ST;Yen, CJ;Yang, CY;Sung, SY;Su, JL
    貢獻者: National Institute of Cancer Research
    摘要: Angiopoietin-like protein 1 (ANGPTL1) has been shown to act as a tumor suppressor by inhibiting angiogenesis, cancer invasion and metastasis. However, little is known about the effects of ANGPTL1 on sorafenib resistance and cancer stem cell properties in hepatocellular carcinoma (HCC) and the mechanism underlying these effects. Here, we show that ANGPTL1 expression positively correlates with sorafenib sensitivity in HCC cells and human HCC tissues. ANGPTL1 significantly decreases epithelial-mesenchymal transition (EMT)-driven sorafenib resistance, cancer stemness and tumor growth of HCC cells by repressing Slug expression. ANGPTL1 directly interacts with and inactivates MET receptor, which contributes to Slug suppression through inhibition of the ERK/AKT-dependent Egr-1 pathway. ANGPTL1 expression inversely correlates with Slug expression, poor sorafenib responsiveness and poor clinical outcomes in HCC patients. CONCLUSIONS: ANGPTL1 inhibits sorafenib resistance and cancer stemness in HCC cells by repressing EMT via inhibition of the MET receptor-AKT/ERK-Egr-1-Slug signaling cascade. ANGPTL1 may serve as a novel MET receptor inhibitor for advanced HCC therapy. This article is protected by copyright.
    日期: 2016-11
    關聯: Hepatology. 2016Nov;64(5):1637-1651.
    Link to: http://dx.doi.org/10.1002/hep.28773
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0270-9139&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000387464200027
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84988805400
    顯示於類別:[蘇振良] 期刊論文

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