首页|WNT/β-catenin signaling in hepatocellular carcinoma:The aberrant activation,pathogenic roles,and therapeutic opportunities
WNT/β-catenin signaling in hepatocellular carcinoma:The aberrant activation,pathogenic roles,and therapeutic opportunities
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Hepatocellular carcinoma(HCC)is a liver cancer,highly heterogeneous both at the histopathological and molecular levels.It arises from hepatocytes as the result of the accumu-lation of numerous genomic alterations in various signaling pathways,including canonical WNT/β-catenin,AKT/mTOR,MAPK pathways as well as signaling associated with telomere maintenance,p53/cell cycle regulation,epigenetic modifiers,and oxidative stress.The role of WNT/β-catenin signaling in liver homeostasis and regeneration is well established,whereas in development and progression of HCC is extensively studied.Herein,we review recent ad-vances in our understanding of how WNT/β-catenin signaling facilitates the HCC development,acquisition of stemness features,metastasis,and resistance to treatment.We outline genetic and epigenetic alterations that lead to activated WNT/β-catenin signaling in HCC.We discuss the pivotal roles of CTNNB1 mutations,aberrantly expressed non-coding RNAs and complexity of crosstalk between WNT/β-catenin signaling and other signaling pathways as challenging or advantageous aspects of therapy development and molecular stratification of HCC patients for treatment.
Cancer stem cellsCTNNB1 mutationsLiver cancerNon-coding RNATumor heterogeneity
Anna Gajos-Michniewicz、Malgorzata Czyz
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Department of Molecular Biology of Cancer,Medical University of Lodz,Lodz 92-215,Poland
research funding of the Medical University of Lódz
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