title: Enhancement of canonical Wnt/β-catenin signaling activity by HCV core protein promotes cell growth of hepatocellular carcinoma cells.
abstract: BACKGROUND
  The Hepatitis C virus (HCV) core protein has been implicated as a potential oncogene or a cofactor in HCV-related hepatocellular carcinoma (HCC), but the underlying mechanisms are unknown. Overactivation of the Wnt/β-catenin signaling is a major factor in oncogenesis of HCC. However, the pathogenesis of HCV core-associated Wnt/β-catenin activation remains to be further characterized. Therefore, we attempted to determine whether HCV core protein plays an important role in regulating Wnt/β-catenin signaling in HCC cells.
  
  
  METHODS
  Wnt/β-catenin signaling activity was investigated in core-expressing hepatoma cells. Protein and gene expression were examined by Western blot, immunofluorescence staining, RT-qPCR, and reporter assay.
  
  
  RESULTS
  HCV core protein significantly enhances Tcf-dependent transcriptional activity induced by Wnt3A in HCC cell lines. Additionally, core protein increases and stabilizes β-catenin levels in hepatoma cell line Huh7 through inactivation of GSK-3β, which contributes to the up-regulation of downstream target genes, such as c-Myc, cyclin D1, WISP2 and CTGF. Also, core protein increases cell proliferation rate and promotes Wnt3A-induced tumor growth in the xenograft tumor model of human HCC.
  
  
  CONCLUSIONS
  HCV core protein enhances Wnt/β-catenin signaling activity, hence playing an important role in HCV-associated carcinogenesis.
authors: The Second Affiliated Hospital and the Key Laboratory of Molecular Biology of Infectious Diseases designated by the Chinese Ministry of Education, Chongqing Medical University, Chongqing, China.
authors: Jiao
authors: J
authors: Liu
authors: Xiong
authors: X
authors: Ding
authors: Jia
authors: J
authors: Tang
authors: Youde
authors: Y
authors: Cao
authors: Peng
authors: P
authors: Hu
authors: Fan
authors: F
authors: Zhou
authors: Xiaoliang
authors: X
authors: Shan
authors: Xuefei
authors: X
authors: Cai
authors: Qingmei
authors: Q
authors: Chen
authors: Ning
authors: N
authors: Ling
authors: Bingqiang
authors: B
authors: Zhang
authors: Yang
authors: Y
authors: Bi
authors: Ke
authors: K
authors: Chen
authors: Hong
authors: H
authors: Ren
authors: Ailong
authors: A
authors: Huang
authors: Tong-Chuan
authors: TC
authors: He
authors: Ni
authors: N
authors: Tang
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000473:pathology*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D016174:Hepacivirus; D006801:Humans; D008113:Liver Neoplasms / Q000473:pathology*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D055550:Protein Stability; D015398:Signal Transduction / Q000187:drug effects; D014158:Transcription, Genetic / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects; D014758:Viral Core Proteins / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D060509:Wnt3A Protein / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D023041:Xenograft Model Antitumor Assays; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D014758:Viral Core Proteins; D060509:Wnt3A Protein; D051176:beta Catenin; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; D038362:Glycogen Synthase Kinase 3