These authors contributed equally to this study.
Article first published online: 14 SEP 2009
Copyright © 2009 American Association for the Study of Liver Diseases
Volume 51, Issue 2, pages 535–544, February 2010
How to Cite
Feng, Y.-X., Zhao, J.-S., Li, J.-J., Wang, T., Cheng, S.-Q., Yuan, Y., Wang, F., Wang, X.-F. and Xie, D. (2010), Liver cancer: EphrinA2 promotes tumorigenicity through Rac1/Akt/NF-κB signaling pathway 120: . Hepatology, 51: 535–544. doi: 10.1002/hep.23313
Potential conflict of interest: Nothing to report.
This is a corrected version of the title first published on 16 November 2009 — the corrected version appears in print. In the originally published version, “akt” was misspelled as “ak”.
- Issue published online: 25 JAN 2010
- Article first published online: 14 SEP 2009
- Accepted manuscript online: 14 SEP 2009 12:00AM EST
- Manuscript Accepted: 29 AUG 2009
- Manuscript Received: 21 MAY 2009
- Ministry of Science and Technology Key program. Grant Numbers: 2008ZX10002-017, 863 Program 2007AA02Z4, 973 Program 2007CB914704
- National Natural Science Funds for Distinguished Young Scholar. Grant Number: 30725010
- National Natural Science Foundation of China. Grant Numbers: 90813023, 30528003
- Chinese Academy of Sciences. Grant Numbers: KSCX2-YW-R-152, KSCX-YW-R-73
- Science and Technology Commission of Shanghai Municipality. Grant Number: 08140902300
Eph/Ephrin family, one of the largest receptor tyrosine kinase families, has been extensively studied in morphogenesis and neural development. Recently, growing attention has been paid to its role in the initiation and progression of various cancers. However, the role of Eph/Ephrins in hepatocellular carcinoma (HCC) has been rarely investigated. In this study, we found that the expression of EphrinA2 was significantly up-regulated in both established cell lines and clinical tissue samples of HCC, and the most significant increase was observed in the tumors invading the portal veins. Forced expression of EphrinA2 in HCC cells significantly promoted in vivo tumorigenicity, whereas knockdown of this gene inhibited this oncogenic effect. We further found that suppression of apoptosis, rather than accelerating proliferation, was responsible for EphrinA2-enhanced tumorigenicity. In addition, EphrinA2 endowed cancer cells with resistance to tumor necrosis factor alpha (TNF-α)–induced apoptosis, thus facilitating their survival. Furthermore, we disclosed a novel EphrinA2/ras-related c3 botulinum toxin substrate 1 (Rac1)/V-akt murine thymoma viral oncogene homolog (Akt)/nuclear factor-kappa B (NF-κB) pathway contributing to the inhibitory effect on apoptosis in HCC cells. Conclusion: This study revealed that EphrinA2 played an important role in the development and progression of HCC by promoting the survival of cancer cells, indicating its role as a potential therapeutic target in HCC. (HEPATOLOGY 2010.)