Aberrant regulation of Wnt signaling in hepatocellular carcinoma
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摘要
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.
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.
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.
引文
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