title: Up-regulation of human cervical cancer proto-oncogene contributes to hepatitis B virus-induced malignant transformation of hepatocyte by down-regulating E-cadherin.
abstract: Hepatocellular carcinoma (HCC) is one of the most fatal human malignancies, Human cervical cancer proto-oncogene (HCCR) aberrantly expressed in a number of malignant tumors, including HCC. HCC is associated with Hepatitis B virus (HBV) infection in a large percentage of cases. To explore the regulation and function of HCCR expression in the development of HCC, we detected HCCR expression in HBV expressing hepatocytes. Results showed that the expression of HCCR was higher in HBV-expressing hepatocytes than that in control cells. Examining different components of HBV revealed that the HBx promotes HCCR expression in hepatocytes via the T-cell factor (TCF)/β-catenin pathway. HCCR expression in HBx transgenic mice increased with as the mice aged and developed tumors. We also found that overexpression of HCCR in hepatocytes promoted cell proliferation, migration, and invasion and reduced cell adhesion. Suppressing HCCR expression abolished the effect of HBx-induced hepatocyte growth. In addition, HCCR represses the expression of E-cadherin by inhibition its promoter activity, which might correlate with the effects of HCCR in hepatocytes. Taken together, these results demonstrate that HBx-HCCR-E-cadherin regulation pathway might play an important role in HBV-induced hepatocarcinogenesis. They also imply that HCCR is a potential risk marker for HCC and/or a potential therapeutic target.
authors.affiliation: State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China.
authors.forename: Junfeng
authors.initials: J
authors.lastname: Li
authors.affiliation: State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China.
authors.forename: Xiaopeng
authors.initials: X
authors.lastname: Dai
authors.affiliation: State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China.
authors.forename: Hongfei
authors.initials: H
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China.
authors.forename: Shihui
authors.initials: S
authors.lastname: Sun
authors.affiliation: State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China.
authors.forename: Tongtong
authors.initials: T
authors.lastname: Gao
authors.affiliation: State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China.
authors.forename: Zhihua
authors.initials: Z
authors.lastname: Kou
authors.affiliation: State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Yu
authors.affiliation: State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Laboratory of Viral Immunology, Lindsley F. Kimball Research Institute, New York Blood Center, New York, NY, USA.
authors.forename: Lanying
authors.initials: L
authors.lastname: Du
authors.affiliation: Laboratory of Viral Immunology, Lindsley F. Kimball Research Institute, New York Blood Center, New York, NY, USA.|Key Laboratory of Medical Molecular Virology of Ministries of Education and Health, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: Shibo
authors.initials: S
authors.lastname: Jiang
authors.affiliation: Department of Biological Sciences, The University of Texas at El Paso, El Paso, TX, USA.
authors.forename: Jianying
authors.initials: J
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China.
authors.forename: Yusen
authors.initials: Y
authors.lastname: Zhou
mesh_terms: D000818:Animals; D015703:Antigens, CD; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D002448:Cell Adhesion; D002465:Cell Movement; D049109:Cell Proliferation; D002472:Cell Transformation, Viral; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D056945:Hep G2 Cells; D006515:Hepatitis B virus / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D022781:Hepatocytes / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D008822:Mice, Transgenic; D009361:Neoplasm Invasiveness; D011401:Promoter Regions, Genetic; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D051820:TCF Transcription Factors / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D054334:Viral Regulatory and Accessory Proteins; D014779:Virus Replication; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism
chemical_list: D015703:Antigens, CD; C513384:CDH1 protein, human; C495270:CTNNB1 protein, human; D015820:Cadherins; C476732:LETMD1 protein, human; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D051820:TCF Transcription Factors; D015534:Trans-Activators; D054334:Viral Regulatory and Accessory Proteins; D051176:beta Catenin; C057628:hepatitis B virus X protein
keywords: E-cadherin; TCF/β-catenin pathway; hepatitis B virus; hepatocellular carcinoma; human cervical cancer proto-oncogene