title: Glucose-regulated protein 94 mediates metastasis by CCT8 and the JNK pathway in hepatocellular carcinoma.
abstract: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer death worldwide. Cancer metastasis is a major obstacle in clinical cancer therapy. The mechanisms underlying the metastasis of HCC remain unclear. Glucose-regulated protein 94 (GRP94) is a key protein involved in mediating cancer progression, and it is highly expressed in HCC specimens. However, the role of GRP94 in cancer metastasis is unclear. A specific short hairpin RNA (shRNA) was employed to knock down GRP94 gene expression in HCC cell lines. Wound-healing migration, transwell migration, and invasion assays were performed to determine the migration and invasive ability of HCC cells. We demonstrated that silencing GRP94 inhibited HCC cell wound healing, migration, and invasion. Furthermore, our findings indicated that GRP94 knockdown might attenuate HCC cell metastasis by inhibiting CCT8/c-Jun/EMT signaling. Our study indicated that silencing GRP94 significantly reduced the migration and invasion abilities of HCC cells. Moreover, depleting GRP94 inhibited cell migration and invasion by downregulating CCT8/c-Jun signaling. Thus, our data suggest that the GRP94/CCT8/c-Jun/EMT signaling cascade might be a new therapeutic target for HCC.
authors.affiliation: Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.|Department of Surgery, College of Medicine, Taipei Medical University, Taipei, Taiwan.|Department of Surgery, Taipei Medical University Hospital, Taipei, Taiwan.|Cancer Research Center, Taipei Medical University Hospital, Taipei, Taiwan.
authors.forename: Po-Li
authors.initials: PL
authors.lastname: Wei
authors.affiliation: Division of General Surgery, Department of Surgery, Shuang Ho Hospital, Taipei Medical University, Taipei, Taiwan.
authors.forename: Chien-Yu
authors.initials: CY
authors.lastname: Huang
authors.affiliation: Division of Hematology and Oncology, Department of Internal Medicine, Taipei Medical University Hospital, Taipei, Taiwan.|Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
authors.forename: Cheng-Jeng
authors.initials: CJ
authors.lastname: Tai
authors.affiliation: Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.|Mongolian National University of Medical Sciences, Ulaanbaatar Mongolia; National Dermatology Center, Ulaanbaatar, Mongolia.
authors.forename: Uyanga
authors.initials: U
authors.lastname: Batzorig
authors.affiliation: Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
authors.forename: Wan-Li
authors.initials: WL
authors.lastname: Cheng
authors.affiliation: Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan. mthuant@tmu.edu.tw.|Department of Surgery, College of Medicine, Taipei Medical University, Taipei, Taiwan. mthuant@tmu.edu.tw.|Department of Surgery, Taipei Medical University Hospital, Taipei, Taiwan. mthuant@tmu.edu.tw.|Division of General Surgery, Department of Surgery, Shuang Ho Hospital, Taipei Medical University, Taipei, Taiwan. mthuant@tmu.edu.tw.
authors.forename: Ming-Te
authors.initials: MT
authors.lastname: Hunag
authors.affiliation: Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan. r5424012@tmu.edu.tw.|Department of Surgery, College of Medicine, Taipei Medical University, Taipei, Taiwan. r5424012@tmu.edu.tw.|Department of Surgery, Taipei Medical University Hospital, Taipei, Taiwan. r5424012@tmu.edu.tw.|Cancer Research Center, Taipei Medical University Hospital, Taipei, Taiwan. r5424012@tmu.edu.tw.
authors.forename: Yu-Jia
authors.initials: YJ
authors.lastname: Chang
mesh_terms: D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism / Q000556:secondary; D045744:Cell Line, Tumor; D054443:Cell Migration Assays; D002465:Cell Movement / Q000235:genetics; D056404:Chaperonin Containing TCP-1 / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D055785:Gene Knockdown Techniques; D020868:Gene Silencing; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics*; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008565:Membrane Proteins / Q000235:genetics*; D009361:Neoplasm Invasiveness / Q000235:genetics; D034741:RNA, Small Interfering; D014945:Wound Healing / Q000235:genetics
chemical_list: D018840:HSP70 Heat-Shock Proteins; D008565:Membrane Proteins; D034741:RNA, Small Interfering; C018551:glucose-regulated proteins; D048031:JNK Mitogen-Activated Protein Kinases; C000610437:CCT8 protein, human; D056404:Chaperonin Containing TCP-1
keywords: CCT8; GRP94; HCC; Metastasis