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 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/Ca(2+) 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.
Li-Juan Liu, Ya-Tang Chen, Fan Zhu, Department of Medical Microbiology, School of Medicine, Wuhan University, Wuhan 430071, Hubei Province, China.
Li-Juan
LJ
Liu
Li-Juan Liu, Ya-Tang Chen, Fan Zhu, Department of Medical Microbiology, School of Medicine, Wuhan University, Wuhan 430071, Hubei Province, China.
Shui-Xiang
SX
Xie
Li-Juan Liu, Ya-Tang Chen, Fan Zhu, Department of Medical Microbiology, School of Medicine, Wuhan University, Wuhan 430071, Hubei Province, China.
Ya-Tang
YT
Chen
Li-Juan Liu, Ya-Tang Chen, Fan Zhu, Department of Medical Microbiology, School of Medicine, Wuhan University, Wuhan 430071, Hubei Province, China.
Jing-Ling
JL
Xue
Li-Juan Liu, Ya-Tang Chen, Fan Zhu, Department of Medical Microbiology, School of Medicine, Wuhan University, Wuhan 430071, Hubei Province, China.
Chuan-Jie
CJ
Zhang
Li-Juan Liu, Ya-Tang Chen, Fan Zhu, Department of Medical Microbiology, School of Medicine, Wuhan University, Wuhan 430071, Hubei Province, China.
Fan
F
Zhu
D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D049109:Cell Proliferation; D003593:Cytoplasm / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006509:Hepatitis B / Q000150:complications; D006515:Hepatitis B virus; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism*; D015398:Signal Transduction; D060449:Wnt Signaling Pathway; D051155:Wnt1 Protein / Q000378:metabolism; D014981:Xenopus; D051176:beta Catenin / Q000378:metabolism
D014408:Biomarkers, Tumor; C495270:CTNNB1 protein, human; C495247:WNT1 protein, human; D051155:Wnt1 Protein; D051176:beta Catenin
Canonical wingless/int-1 signaling; Catenin β1; Crosstalk; Hepatocellular carcinoma; Non-canonical wingless/int-1 signaling; Wingless/int-1
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