Tags

Type your tag names separated by a space and hit enter

Enhancement of canonical Wnt/β-catenin signaling activity by HCV core protein promotes cell growth of hepatocellular carcinoma cells.
PLoS One 2011; 6(11):e27496Plos

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.

METHODOLOGY

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.

PRINCIPAL FINDINGS

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/SIGNIFICANCE

HCV core protein enhances Wnt/β-catenin signaling activity, hence playing an important role in HCV-associated carcinogenesis.

Authors+Show Affiliations

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.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22110662

Citation

Liu, Jiao, et al. "Enhancement of Canonical Wnt/β-catenin Signaling Activity By HCV Core Protein Promotes Cell Growth of Hepatocellular Carcinoma Cells." PloS One, vol. 6, no. 11, 2011, pp. e27496.
Liu J, Ding X, Tang J, et al. Enhancement of canonical Wnt/β-catenin signaling activity by HCV core protein promotes cell growth of hepatocellular carcinoma cells. PLoS ONE. 2011;6(11):e27496.
Liu, J., Ding, X., Tang, J., Cao, Y., Hu, P., Zhou, F., ... Tang, N. (2011). Enhancement of canonical Wnt/β-catenin signaling activity by HCV core protein promotes cell growth of hepatocellular carcinoma cells. PloS One, 6(11), pp. e27496. doi:10.1371/journal.pone.0027496.
Liu J, et al. Enhancement of Canonical Wnt/β-catenin Signaling Activity By HCV Core Protein Promotes Cell Growth of Hepatocellular Carcinoma Cells. PLoS ONE. 2011;6(11):e27496. PubMed PMID: 22110662.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Enhancement of canonical Wnt/β-catenin signaling activity by HCV core protein promotes cell growth of hepatocellular carcinoma cells. AU - Liu,Jiao, AU - Ding,Xiong, AU - Tang,Jia, AU - Cao,Youde, AU - Hu,Peng, AU - Zhou,Fan, AU - Shan,Xiaoliang, AU - Cai,Xuefei, AU - Chen,Qingmei, AU - Ling,Ning, AU - Zhang,Bingqiang, AU - Bi,Yang, AU - Chen,Ke, AU - Ren,Hong, AU - Huang,Ailong, AU - He,Tong-Chuan, AU - Tang,Ni, Y1 - 2011/11/15/ PY - 2011/07/04/received PY - 2011/10/18/accepted PY - 2011/11/24/entrez PY - 2011/11/24/pubmed PY - 2012/3/27/medline SP - e27496 EP - e27496 JF - PloS one JO - PLoS ONE VL - 6 IS - 11 N2 - 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. METHODOLOGY: 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. PRINCIPAL FINDINGS: 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/SIGNIFICANCE: HCV core protein enhances Wnt/β-catenin signaling activity, hence playing an important role in HCV-associated carcinogenesis. SN - 1932-6203 UR - https://www.unboundmedicine.com/medline/citation/22110662/Enhancement_of_canonical_Wnt/β_catenin_signaling_activity_by_HCV_core_protein_promotes_cell_growth_of_hepatocellular_carcinoma_cells_ L2 - http://dx.plos.org/10.1371/journal.pone.0027496 DB - PRIME DP - Unbound Medicine ER -