Aberrant regulation of Wnt signaling in hepatocellular carcinoma

Hepatocellular carcinoma(HCC) is one of the most lethal malignancies in the world. Several signaling pathways,including the wingless/int-1(Wnt) signaling pathway,have been shown to be commonly activated in HCC. The Wnt signaling pathway can be triggered via both catenin β1(CTNNB1)-dependent(also kno...

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Published inWorld journal of gastroenterology : WJG Vol. 22; no. 33; pp. 7486 - 7499
Main Authors Liu, Li-Juan, Xie, Shui-Xiang, Chen, Ya-Tang, Xue, Jing-Ling, Zhang, Chuan-Jie, Zhu, Fan
Format Journal Article
LanguageEnglish
Published United States Baishideng Publishing Group Inc 07.09.2016
Subjects
Animals
beta Catenin - metabolism
Biomarkers, Tumor - metabolism
Carcinoma, Hepatocellular - metabolism
carcinoma;Wingless/int-1;Catenin
Cell Proliferation
Cytoplasm - metabolism
Gene Expression Regulation, Neoplastic
Hepatitis B - complications
Hepatitis B virus
Hepatocellular
Humans
Liver Neoplasms - metabolism
Review
Signal Transduction
signaling
signaling;Non-canonical
wingless/int-1
Wnt Signaling Pathway
Wnt1 Protein - metabolism
Xenopus
β1;Crosstalk;Canonical
Canonical wingless/int-1 signaling
Hepatocellular carcinoma
Non-canonical wingless/int-1 signaling
Wingless/int-1
Crosstalk
Catenin β1
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Summary:Hepatocellular carcinoma(HCC) is one of the most lethal malignancies in the world. Several signaling pathways,including the wingless/int-1(Wnt) signaling pathway,have been shown to be commonly activated in HCC. The Wnt signaling pathway can be triggered via both catenin β1(CTNNB1)-dependent(also known as 'canonical') and CTNNB1-independent(often referred to as 'non-canonical') pathways. Specifically,the canonical Wnt pathway is one of those most frequently reported in HCC. Aberrant regulation from three complexes(the cell-surface receptor complex,the cytoplasmic destruction complex and the nuclear CTNNB1/T-cell-specific transcription factor/lymphoid enhancer binding factor transcriptional complex) are all involved in HCC. Although the non-canonical Wnt pathway is rarely reported,two main non-canonical pathways,Wnt/planar cell polarity pathway and Wnt/Ca2+ pathway,participate in the regulation of hepatocarcinogenesis. Interestingly,the canonical Wnt pathway is antagonized by non-canonical Wnt signaling in HCC. Moreover,other signaling cascades have also been demonstrated to regulate the Wnt pathway through crosstalk in HCC pathogenesis. This review provides a perspective on the emerging evidence that the aberrant regulation of Wnt signaling is a critical mechanism for the development of HCC. Furthermore,crosstalk between different signaling pathways might be conducive to the development of novel molecular targets of HCC.
Bibliography:Li-Juan Liu;Shui-Xiang Xie;Ya-Tang Chen;Jing-Ling Xue;Chuan-Jie Zhang;Fan Zhu;Department of Medical Microbiology,School of Medicine,Wuhan University;Department of Pathogenic Biology,Gannan Medical University;Department of Pathology,School of Medicine,Wuhan University;Department of Children Health Care,Wuhan Medical Care Center for Women and Children;Hubei Province Key Laboratory of Allergy and Immunology
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Supported by National Natural Science Foundation of China, No. 31470264 and No. 81502418; the Key Program of Natural Science Foundation of Hubei Province of China, No. 2014CFA078; the Hubei Provincial Natural Science Foundation of China, No. 2015CFB168 and No. 2012FFB04304; the Scientific Research Innovation Team in Hubei, No. 2015CFA009; the General Financial Grant from the China Postdoctoral Science Foundation, No. 2014M550411; the Fundamental Research Funds for the Central Universities, No. 2042014kf0029; the Tianqing Liver Disease Research Fund of the China Foundation for Hepatitis Prevention and Control, No. TQGB20140250; the Innovation Seed Fund of Wuhan University School of Medicine; the Science and Technology Department Supported Program of Jiangxi Province of China, No. 2010BSA13500; the Science and Technology Project of Education Department of Jiangxi Province of China, No. GJJ11570.
Correspondence to: Fan Zhu, PhD, Professor, Department of Medical Microbiology, School of Medicine, Wuhan University, 185 Donghu Road, Wuhan 430071, Hubei Province, China. fanzhu@whu.edu.cn
Telephone: +86-27-68759906 Fax: +86-27-68759906
Author contributions: Liu LJ and Xie SX equally contributed to this paper with literature review and editing; Chen YT participated in drawing the graphs of the signaling pathways; Xue JL prepared a draft of the “canonical Wnt signaling” portion; Zhang CJ drafted the “non-canonical Wnt signaling” portion; Zhu F was responsible for the design, editing and revision of the article, and approval of the final version.
ISSN:1007-9327
2219-2840
DOI:10.3748/wjg.v22.i33.7486