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As an independent prognostic factor, FAT10 promotes hepatitis B virus-related hepatocellular carcinoma progression via Akt/GSK3β pathway

Oncogene volume 33, pages 909–920 (2014)Cite this article

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Abstract

FAT10 is an oncogene that is localized at 6q21.3, a region frequently amplified in hepatocellular carcinoma (HCC). Recently, growing attention has been paid to its effect in the initiation of various cancers. However, there has been little research into the influence of FAT10 on the progression and prognosis of HCC, especially in hepatitis B virus (HBV)-related HCC. Here, we aimed at investigating clincopathological significance of FAT10 in HBV-related HCC and its underlying mechanisms. Based on the analysis of FAT10 expression in a reliable and large number of cases with 5-year follow-up, we showed that FAT10 was significantly increased in 260 samples from HBV-related HCC patients, compared with 30 normal tissue, 50 cirrhosis and matched adjacent nontumor tissues. FAT10 expression is correlated with recurrence and poor prognosis in HBV-related HCC. In addition, ectopic expression of FAT10 enhanced cell proliferation, inhibited apoptosis and induced cell cycle progression, whereas silencing FAT10 expression suppressed cell proliferation and induced apoptosis. FAT10 also induced the epithelial–mesenchymal transition (EMT) and promoted invasion of HCC cells. Furthermore, we found Akt/GSK3β pathway contributed to the effects of FAT10 in HCC cells. Blocking the Akt pathway significantly inhibited the actions of FAT10. Taken together, the ubiquitin-like protein FAT10 has a central role in regulating diverse aspects of the pathogenesis of HCC, indicating that it might be a potential therapeutic target.

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Acknowledgements

This work was supported by the National Nature Science Foundation of China (Grant No. 81172056 and 81172586).

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Author notes

  1. L Liu and Z Dong: These authors share co-first authorship.

Authors and Affiliations

  1. Hepatology Unit and Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China

    L Liu & Y Ding

  2. Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, China

    Z Dong, J Liang, C Cao, J Sun, Y Ding & D Wu

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  1. L Liu
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Correspondence to L Liu or D Wu.

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Liu, L., Dong, Z., Liang, J. et al. As an independent prognostic factor, FAT10 promotes hepatitis B virus-related hepatocellular carcinoma progression via Akt/GSK3β pathway. Oncogene 33, 909–920 (2014). https://doi.org/10.1038/onc.2013.236

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