Ubiquitin-like Protein FAT10 Promotes the Invasion and Metastasis of Hepatocellular Carcinoma by Modifying β-Catenin Degradation
Ubiquitin-like Protein FAT10 Promotes the Invasion and Metastasis of Hepatocellular Carcinoma by Modifying β-Catenin Degradation
复制标题
泛素样蛋白FAT10通过修饰β-Catenin降解促进肝细胞癌的侵袭和转移
DOI：
10.1158/0008-5472.can-14-0284
复制
发表时间：
2014-09-15
期刊：
影响因子：
11.2
通讯作者：
Shao, Jianghua
中科院分区：
文献类型：
--
作者：
Yuan, Rongfa;Wang, Kai;Shao, Jianghua
泛素样蛋白FAT10和同源盒蛋白HOXB9各自促进肝细胞癌（HCC）的转移进展。在本研究中，我们探讨了FAT10和HOXB9在HCC中的临床病理意义，并探讨了FAT10在HOXB9介导的侵袭和转移中的机制作用。相对于邻近正常组织，FAT10和HOXB9在HCC中明显过表达，其表达与相关恶性特征呈正相关。rnai介导的FAT10沉默降低了HOXB9的表达，抑制了HCC的侵袭和转移。HOXB9过表达可逆转FAT10沉默的作用，而rnai介导的HOXB9沉默可降低由FAT10过表达驱动的HCC侵袭和转移。在机制上，FAT10通过调节β -catenin/TCF4通路，直接结合β -catenin，阻止其泛素化和降解，从而调控HOXB9的表达。总之，我们的研究结果确定了一个涉及FAT10、β -catenin/TCF4和HOXB9的新的HCC调节回路，其功能障碍驱动HCC的侵袭性和转移性特征。(c) 2014年aacr。
The ubiquitin-like protein FAT10 and the homeobox protein HOXB9 each promote metastatic progression in hepatocellular carcinoma (HCC). In this study, we investigated the clinicopathologic significance of FAT10 and HOXB9 in HCC and investigated a mechanistic role for FAT10 in HOXB9-mediated invasiveness and metastasis. Relative to adjacent normal tissues, FAT10 and HOXB9 were markedly overexpressed in HCC, where a positive correlation in their expression and associated malignant characteristics were found. RNAi-mediated silencing of FAT10 decreased HOXB9 expression and inhibited HCC invasion and metastasis in vitro and in vivo. The effects of FAT10 silencing were reversed by HOXB9 overexpression, whereas RNAi-mediated silencing of HOXB9 decreased HCC invasion and metastasis driven by FAT10 overexpression. Mechanistically, FAT10 regulated HOXB9 expression by modulating the beta-catenin/TCF4 pathway, directly binding to beta-catenin and preventing its ubiquitination and degradation. Together, our results identified a novel HCC regulatory circuit involving FAT10, beta-catenin/TCF4, and HOXB9, the dysfunction of which drives invasive and metastatic character in HCC. (C) 2014 AACR.