WNT/β-catenin signaling in hepatocellular carcinoma: The aberrant activation, pathogenic roles, and therapeutic opportunities
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 accumulation of numerous genomic alterations in various signaling pathways, including canonical WNT/β-catenin, AKT/mTOR, MAPK pat...
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| Format: | Article |
| Language: | English |
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KeAi Communications Co., Ltd.
2024-03-01
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| Series: | Genes and Diseases |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352304223001265 |
| _version_ | 1797731018533240832 |
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| author | Anna Gajos-Michniewicz Malgorzata Czyz |
| author_facet | Anna Gajos-Michniewicz Malgorzata Czyz |
| author_sort | Anna Gajos-Michniewicz |
| collection | DOAJ |
| description | 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 accumulation 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 advances 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. |
| first_indexed | 2024-03-12T11:52:56Z |
| format | Article |
| id | doaj.art-5a7595a8525d4da6a00d640674986538 |
| institution | Directory Open Access Journal |
| issn | 2352-3042 |
| language | English |
| last_indexed | 2024-03-12T11:52:56Z |
| publishDate | 2024-03-01 |
| publisher | KeAi Communications Co., Ltd. |
| record_format | Article |
| series | Genes and Diseases |
| spelling | doaj.art-5a7595a8525d4da6a00d6406749865382023-08-31T05:03:04ZengKeAi Communications Co., Ltd.Genes and Diseases2352-30422024-03-01112727746WNT/β-catenin signaling in hepatocellular carcinoma: The aberrant activation, pathogenic roles, and therapeutic opportunitiesAnna Gajos-Michniewicz0Malgorzata Czyz1Department of Molecular Biology of Cancer, Medical University of Lodz, Lodz 92-215, PolandCorresponding author. Department of Molecular Biology of Cancer, Medical University of Lodz, 6/8 Mazowiecka Street, Lodz 92-215, Poland.; Department of Molecular Biology of Cancer, Medical University of Lodz, Lodz 92-215, PolandHepatocellular carcinoma (HCC) is a liver cancer, highly heterogeneous both at the histopathological and molecular levels. It arises from hepatocytes as the result of the accumulation 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 advances 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.http://www.sciencedirect.com/science/article/pii/S2352304223001265Cancer stem cellsCTNNB1 mutationsLiver cancerNon-coding RNATumor heterogeneity |
| spellingShingle | Anna Gajos-Michniewicz Malgorzata Czyz WNT/β-catenin signaling in hepatocellular carcinoma: The aberrant activation, pathogenic roles, and therapeutic opportunities Genes and Diseases Cancer stem cells CTNNB1 mutations Liver cancer Non-coding RNA Tumor heterogeneity |
| title | WNT/β-catenin signaling in hepatocellular carcinoma: The aberrant activation, pathogenic roles, and therapeutic opportunities |
| title_full | WNT/β-catenin signaling in hepatocellular carcinoma: The aberrant activation, pathogenic roles, and therapeutic opportunities |
| title_fullStr | WNT/β-catenin signaling in hepatocellular carcinoma: The aberrant activation, pathogenic roles, and therapeutic opportunities |
| title_full_unstemmed | WNT/β-catenin signaling in hepatocellular carcinoma: The aberrant activation, pathogenic roles, and therapeutic opportunities |
| title_short | WNT/β-catenin signaling in hepatocellular carcinoma: The aberrant activation, pathogenic roles, and therapeutic opportunities |
| title_sort | wnt β catenin signaling in hepatocellular carcinoma the aberrant activation pathogenic roles and therapeutic opportunities |
| topic | Cancer stem cells CTNNB1 mutations Liver cancer Non-coding RNA Tumor heterogeneity |
| url | http://www.sciencedirect.com/science/article/pii/S2352304223001265 |
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