GRP78 Promotes Hepatocellular Carcinoma proliferation by increasing FAT10 expression through the NF-κB pathway
GRP78 Promotes Hepatocellular Carcinoma proliferation by increasing FAT10 expression through the NF-κB pathway
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GRP78 通过 NF-kappa B 途径增加 FAT10 表达，促进肝细胞癌增殖
DOI：
10.1016/j.yexcr.2018.02.007
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发表时间：
2018-04-01
影响因子：
3.7
通讯作者：
Wang, Kai
中科院分区：
文献类型：
--
作者：
Luo, Chenglin;Xiong, Haixia;Wang, Kai
葡萄糖调节蛋白78(GRP78)和泛素样蛋白FAT10各自促进肝细胞癌(HCC)的增殖。然而，GRP78与PATO在肝细胞癌增殖中的关系尚不清楚。在本研究中，我们发现GRP78和PATO在肝细胞癌组织中的表达显著高于癌旁组织，并且它们的表达与相关的增殖特性呈正相关。GRP78和FAT10的高表达与肝细胞癌的肿瘤增殖和预后不良呈正相关。此外，GRP78基因敲除降低了FAT10的表达，并在体内外抑制了肝癌的增殖。GRP78基因下调的作用可以通过上调来挽救，而FAT10基因下调则减少了GRP78上调促进的肝癌细胞的增殖。此外，GRP78通过调节核因子-kappa B通路来调节FAT10的表达，直接激活核因子-kappaB通路增加了FAT10的表达，FAT10是一个对抗抑癌基因p53的基因。综上所述，这些结果表明，这个新发现的GRP78-NF-kappa B-FAT10轴将为理解人类肝细胞癌的增殖调控机制提供新的见解。
Glucose-regulated protein 78(GRP78) and the ubiquitin-like protein FAT10 each promote proliferation in hepatocellular carcinoma(HCC). However, the relationship of GRP78 and PATIO in HCC proliferation are still not known. In this study, we found that GRP78 and PATIO were significantly overexpressed in HCC tissues compare with adjacent non-cancerous tissues, and a positive correlation was found between their expression and associated proliferation characteristics. High expression of GRP78 and FAT10 were positively correlated with tumor proliferation and poor prognosis in HCC. Moreover, GRP78 knockdown reduced FAT10 expression and suppressed HCC proliferation in vitro and in vivo. The effects of GRP78 knockdown were rescued by PATIO up regulation, whereas FAT10 knockdown reduced HCC proliferation enhanced by GRP78 up-regulation. Furthermore, GRP78 modulated FAT10 expression by regulating the NF-kappa B pathway, direct activation of the NF-kappa B pathway increased the expression of FAT10, a gene counteracting the tumor suppressor p53. Taken together, these results suggest that this newly identified GRP78-NF-kappa B-FAT10 axis will provide novel insight into the understanding of the regulatory mechanisms of proliferation in human HCC.