title: Down-regulation of Rab17 promotes tumourigenic properties of hepatocellular carcinoma cells via Erk pathway.
abstract: The small GTPase, Ras-related protein 17 (Rab17), a member of the Rab family, plays a critical role in the regulation of membrane traffic in polarized eukaryotic cells. However, the role of Rab17 in hepatocellular carcinoma (HCC) is not clear. Clinical speciments reveal that Rab17 was present in 15 of 20 (75.0%) paraneoplastic tissues and 7 of 20 (35.0%) HCC samples (P=0.0248). To elucidate the tumourigenic role of Rab17 in HCC, we generated two Rab17 low-expressing HCC cell lines (Hep3B and Huh-7). The results showed that Rab17 down-regulation significantly promoted the tumourigenic properties of HCC cells in vitro and in vivo, as demonstrated by enhanced cell proliferation, colony formation, invasion and migration, decreased G1 arrest, and increased tumour xenograft growth and angiogenesis. However, the enhanced tumourigenic properties of HCC cells by Rab17 down-regulation was significantly inhibited by PD980592, the inhibitor of the Erk pathway, indicating that the Erk pathway plays a critical role in Rab17 down-regulation-induced enhanced tumourigenic properties of HCC cells. Our data provide a new insight into the essential role of Rab17 in HCC carcinogenesis and suggest that Rab17 expression might be tumor suppressor gene and might provide a new interventional therapeutic target for this common malignancy.
authors.affiliation: Department of Intervention, The First Hospital Affiliated to The Xinxiang Medical University Xinxiang, Henan, China.
authors.forename: Jingsong
authors.initials: J
authors.lastname: Qi
authors.affiliation: Department of Intervention, The First Hospital Affiliated to The Xinxiang Medical University Xinxiang, Henan, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Zhao
authors.affiliation: Department of Intervention, The First Hospital Affiliated to The Xinxiang Medical University Xinxiang, Henan, China.
authors.forename: Fenbao
authors.initials: F
authors.lastname: Li
authors.affiliation: Department of Intervention, The First Hospital Affiliated to The Xinxiang Medical University Xinxiang, Henan, China.
authors.forename: Yingchang
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Department of Intervention, The First Hospital Affiliated to The Xinxiang Medical University Xinxiang, Henan, China.
authors.forename: Hongkai
authors.initials: H
authors.lastname: Cui
authors.affiliation: Department of Intervention, The First Hospital Affiliated to The Xinxiang Medical University Xinxiang, Henan, China.
authors.forename: Aiguang
authors.initials: A
authors.lastname: Liu
authors.affiliation: Department of Intervention, The First Hospital Affiliated to The Xinxiang Medical University Xinxiang, Henan, China.
authors.forename: Huajie
authors.initials: H
authors.lastname: Mao
authors.affiliation: Department of Intervention, The First Hospital Affiliated to The Xinxiang Medical University Xinxiang, Henan, China.
authors.forename: Yongli
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Intervention, The First Hospital Affiliated to The Xinxiang Medical University Xinxiang, Henan, China.
authors.forename: Xizhong
authors.initials: X
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D006528:Carcinoma, Hepatocellular / Q000098:blood supply / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D015536:Down-Regulation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D059585:G1 Phase Cell Cycle Checkpoints; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008113:Liver Neoplasms / Q000098:blood supply / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D008297:Male; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D009389:Neovascularization, Pathologic; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D034622:RNA Interference; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D014162:Transfection; D047368:Tumor Burden; D023041:Xenograft Model Antitumor Assays; D020691:rab GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; C081073:rab17 protein, epithelial; D048049:Extracellular Signal-Regulated MAP Kinases; D020691:rab GTP-Binding Proteins
keywords: Rab17; cell polarization; hepatocellular carcinoma cells; interventional therapy; signaling pathway; small GTPase