As an independent prognostic factor, FAT10 promotes hepatitis B virus-related hepatocellular carcinoma progression via Akt/GSK3β pathway
As an independent prognostic factor, FAT10 promotes hepatitis B virus-related hepatocellular carcinoma progression via Akt/GSK3β pathway
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作为独立的预后因素，FAT10 通过 Akt/GSK3β 通路促进乙型肝炎病毒相关的肝细胞癌进展
DOI：
10.1038/onc.2013.236
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发表时间：
2014-02-13
期刊：
影响因子：
8
通讯作者：
Wu, D.
中科院分区：
文献类型：
--
作者：
Liu, L.;Dong, Z.;Wu, D.
FAT10 是一种癌基因，定位于 6q21。 3，是肝细胞癌 (HCC) 中经常扩增的区域。最近，人们越来越关注其在各种癌症发生中的作用。然而，关于FAT10对HCC进展和预后的影响的研究很少，尤其是乙型肝炎病毒（HBV）相关的HCC。在这里，我们的目的是研究 FAT10 在 HBV 相关 HCC 中的临床病理学意义及其潜在机制。基于对 5 年随访的可靠且大量病例的 FAT10 表达分析，我们发现，与 30 个正常组织、50 个肝硬化和匹配的邻近非肿瘤组织相比，260 个 HBV 相关 HCC 患者样本中 FAT10 显着升高。 FAT10 表达与 HBV 相关 HCC 的复发和不良预后相关。此外，FAT10的异位表达增强细胞增殖，抑制细胞凋亡并诱导细胞周期进程，而沉默FAT10表达则抑制细胞增殖并诱导细胞凋亡。 FAT10还诱导上皮-间质转化（EMT）并促进HCC细胞的侵袭。此外，我们发现 Akt/GSK3β 通路有助于 FAT10 在 HCC 细胞中的作用。阻断 Akt 通路可显着抑制 FAT10 的作用。综上所述，泛素样蛋白 FAT10 在调节 HCC 发病机制的各个方面发挥着核心作用，表明它可能是一个潜在的治疗靶点。
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.