These authors contributed equally to this work.
Article first published online: 25 AUG 2011
Copyright © 2011 American Association for the Study of Liver Diseases
Volume 54, Issue 3, pages 910–919, 2 September 2011
How to Cite
Li, H., Ge, C., Zhao, F., Yan, M., Hu, C., Jia, D., Tian, H., Zhu, M., Chen, T., Jiang, G., Xie, H., Cui, Y., Gu, J., Tu, H., He, X., Yao, M., Liu, Y. and Li, J. (2011), Hypoxia-inducible factor 1 alpha–activated angiopoietin-like protein 4 contributes to tumor metastasis via vascular cell adhesion molecule-1/integrin β1 signaling in human hepatocellular carcinoma. Hepatology, 54: 910–919. doi: 10.1002/hep.24479
Potential conflict of interest: Nothing to report.
This work was supported, in part, by grants from the National Key Sci-Tech Special Project of China (grant 2008ZX10002-022), the National Key Program for Basic Research of China (973) (2009CB521803), the Program Of Shanghai Subject Chief Scientist (A) (09XD1403600), Shanghai Science and Technology Developing Program (07DJ14006), and Shanghai Natural Science Foundation (08ZR1418300).
- Issue published online: 25 AUG 2011
- Article first published online: 25 AUG 2011
- Accepted manuscript online: 14 JUN 2011 08:07AM EST
- Manuscript Accepted: 26 MAY 2011
- Manuscript Received: 28 FEB 2011
- National Key Sci-Tech Special Project of China. Grant Number: 2008ZX10002-022
- National Key Program for Basic Research of China. Grant Number: (973) (2009CB521803)
- Program Of Shanghai Subject Chief Scientist. Grant Number: (A) (09XD1403600)
- Shanghai Science and Technology Developing Program. Grant Number: (07DJ14006)
- Shanghai Natural Science Foundation. Grant Number: (08ZR1418300)
Correction: Corrections: Hypoxia-inducible factor 1 alpha–activated angiopoietin-like protein 4 contributes to tumor metastasis via vascular cell adhesion molecule-1/integrin β1 signaling in human hepatocellular carcinoma
Vol. 54, Issue 6, 2280, Article first published online: 30 NOV 2011
Angiopoietin-like protein 4 (ANGPTL4) plays complex and often contradictory roles in vascular biology and tumor metastasis, but little is known about its function in hepatocellular carcinoma (HCC) metastasis. In the present study, we showed that hypoxia-inducible factor 1α (HIF-1α) directly up-regulates ANGPTL4, and its stableness positively correlates with ANGPTL4 expression in HCC tissue. Overexpression of ANGPTL4 significantly increased HCC cell transendothelial migration in vitro and intrahepatic and distal pulmonary metastasis in vivo, whereas silencing ANGPTL4 expression or treatment with a neutralizing antibody specific for ANGPTL4 protein resulted in a reduced transendothelial migration. We also found that serum ANGPTL4 is higher in HCC patients, compared to healthy control, and correlates with intrahepatic metastasis and histological grade. Further, secreted ANGPTL4 promotes transendothelial migration and metastasis of HCC cells in vitro and in vivo through the up-regulation of vascular cell adhesion molecule-1 (VCAM-1) of human umbilical vein endothelial cells and the activation of the VCAM-1/integrin β1 axis. Conclusion: ANGPTL4 is a target gene of HIF-1α and acts as an important regulator in the metastasis of HCC. Serum ANGPTL4 correlates with tumor progression and metastasis and might be used to indicate prognosis in HCC patients. (HEPATOLOGY 2011 54:910–919;)