下调和上调
癌症研究
血管生成
转移
蛋白激酶B
车站3
信号转导
新生血管
细胞迁移
MAPK/ERK通路
整合素
异位表达
原癌基因酪氨酸蛋白激酶Src
生物
癌症
医学
细胞
细胞生物学
细胞培养
内科学
遗传学
基因
生物化学
作者
Qian Yan,Lingxi Jiang,Ming Liu,Dandan Yu,Yu Zhang,Yan Li,Shuo Fang,Yan Li,Ying–Hui Zhu,Yufeng Yuan,Xin‐Yuan Guan
出处
期刊:Cancer Research
[American Association for Cancer Research]
日期:2017-09-13
卷期号:77 (21): 5831-5845
被引量:61
标识
DOI:10.1158/0008-5472.can-17-0579
摘要
Downregulation of tumor suppressor signaling plays an important role in the pathogenesis of hepatocellular carcinoma (HCC). Here, we report that downregulation of the angiopoietin-like protein ANGPTL1 is associated with vascular invasion, tumor thrombus, metastasis, and poor prognosis in HCC. Ectopic expression of ANGPTL1 in HCC cells effectively decreased their in vitro and in vivo tumorigenicity, cell motility, and angiogenesis. shRNA-mediated depletion of ANGPTL1 exerted opposing effects. ANGPTL1 promoted apoptosis via inhibition of the STAT3/Bcl-2-mediated antiapoptotic pathway and decreased cell migration and invasion via downregulation of transcription factors SNAIL and SLUG. Furthermore, ANGPTL1 inhibited angiogenesis by attenuating ERK and AKT signaling and interacted with integrin α1β1 receptor to suppress the downstream FAK/Src-JAK-STAT3 signaling pathway. Taken together, these results suggest ANGPTL1 as a prognostic biomarker and novel therapeutic agent in HCC. Cancer Res; 77(21); 5831-45. ©2017 AACR.
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