title: P4HB promotes HCC tumorigenesis through downregulation of GRP78 and subsequent upregulation of epithelial-to-mesenchymal transition.
abstract: 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.
authors.affiliation: Department of Nuclear Medicine, Seventh People's Hospital of Shanghai University of TCM, Shanghai, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Xia
authors.affiliation: Department of Nuclear Medicine, Seventh People's Hospital of Shanghai University of TCM, Shanghai, China.
authors.forename: Juhua
authors.initials: J
authors.lastname: Zhuang
authors.affiliation: Department of Nuclear Medicine, Seventh People's Hospital of Shanghai University of TCM, Shanghai, China.
authors.forename: Guoyu
authors.initials: G
authors.lastname: Wang
authors.affiliation: Department of Nuclear Medicine, Seventh People's Hospital of Shanghai University of TCM, Shanghai, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Ni
authors.affiliation: Department of Integrated TCM & western medcine, President's Office of Seventh People's Hospital of Shanghai University of TCM, Shanghai, China.
authors.forename: Jiening
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Nuclear Medicine, Seventh People's Hospital of Shanghai University of TCM, Shanghai, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Ye
mesh_terms: D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000201:enzymology* / Q000235:genetics / Q000473:pathology / Q000517:prevention & control; D002465:Cell Movement; D049109:Cell Proliferation; D000091342:Endoplasmic Reticulum Chaperone BiP; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D056945:Hep G2 Cells; D006801:Humans; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology / Q000517:prevention & control; D008297:Male; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D011393:Procollagen-Proline Dioxygenase / Q000235:genetics / Q000378:metabolism*; D019704:Protein Disulfide-Isomerases / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D015398:Signal Transduction; D013997:Time Factors; D014162:Transfection
chemical_list: D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; C000717248:Hspa5 protein, mouse; D011393:Procollagen-Proline Dioxygenase; C526497:P4HB protein, human; D019704:Protein Disulfide-Isomerases
keywords: GRP78; P4HB; epithelial-to-mesenchymal transition; hepatocellular carcinoma; tumorigenesis