期刊
ONCOTARGET
卷 8, 期 5, 页码 8512-8521出版社
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.14337
关键词
P4HB; GRP78; hepatocellular carcinoma; tumorigenesis; epithelial-to-mesenchymal transition
资金
- Natural Science Foundation of China [81371597, 81571718]
- Shanghai Sailing Program [16YF1408800]
- Shanghai Pudong Science and Technology Committee Foundation [PKJ2016-Y50]
- Key disciplines Group Constraction Project of Pudong Health Burea of Shanghai [PWZxq2014-12]
P4HB and GRP78 are molecular chaperones involved in cellular response to ER stress. They have been linked to cancer progression; however, their roles in hepatocellular carcinoma (HCC) are largely unclear. In this study, we found that P4HB is overexpressed in human HCC tissues and cell lines. Higher tumoral P4HB levels are correlated with more advanced disease and poorer survival. GRP78 expression is inversely correlated with P4HB in human HCC tissues, and downregulated by P4HB in HCC cell lines. P4HB overexpression promotes HCC cell growth, migration, invasion and epithelial-to-mesenchymal transition (EMT) in vitro. GRP78 overexpression not only inhibits HCC cell growth, migration, invasion and EMT, but also antagonizes the oncogenic effects of P4HB overexpression. Furthermore, P4HB silencing inhibits HCC tumorigenesis in vivo. Taken together, our results provided evidence that P4HB promotes HCC progression through downregulation of GRP78 and subsequent upregulation of EMT.
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