ANGPTL1 interacts with integrin α1β1 to suppress HCC angiogenesis and metastasis by inhibiting JAK2/STAT3 signaling

Yan，Qian1,2; Jiang，Lingxi1,2; Liu，Ming1,2,3,4; Yu，Dandan1,2; Zhang，Yu1,2; Li，Yan1,2,5; Fang，Shuo1,2; Li，Yan6; Zhu，Ying Hui6; Yuan，Yun Fei6; Guan，Xin Yuan1,2,6

2017-11-01

10.1158/0008-5472.CAN-17-0579

CANCER RESEARCH   影响因子和分区

0008-5472

1538-7445

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 a1b1 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.

SCI

英语

其他

WOS:000414248300045

CLINICAL MEDICINE

2-s2.0-85035041353

Scopus

1.,Department of Clinical Oncology,University of Hong Kong,Hong Kong,Hong Kong
2.,State Key Laboratory for Liver Research,University of Hong Kong,Hong Kong,Hong Kong
3.,Key Laboratory of Protein Modification and Degradation,School of Basic Medical Sciences,Guangzhou Medical University,Guangzhou,China
4.,Affiliated Cancer Hospital,Guangzhou Medical University,Guangzhou,China
5.,Department of Biology,South University of Science and Technology of China,Shenzhen,China
6.,State Key Laboratory of Oncology in Southern China,Sun Yat-sen University Cancer Center,Guangzhou,China

Yan，Qian,Jiang，Lingxi,Liu，Ming,et al. ANGPTL1 interacts with integrin α1β1 to suppress HCC angiogenesis and metastasis by inhibiting JAK2/STAT3 signaling[J]. CANCER RESEARCH,2017,77(21):5831-5845.

Yan，Qian.,Jiang，Lingxi.,Liu，Ming.,Yu，Dandan.,Zhang，Yu.,...&Guan，Xin Yuan.(2017).ANGPTL1 interacts with integrin α1β1 to suppress HCC angiogenesis and metastasis by inhibiting JAK2/STAT3 signaling.CANCER RESEARCH,77(21),5831-5845.

Yan，Qian,et al."ANGPTL1 interacts with integrin α1β1 to suppress HCC angiogenesis and metastasis by inhibiting JAK2/STAT3 signaling".CANCER RESEARCH 77.21(2017):5831-5845.