期刊
NATURE REVIEWS GASTROENTEROLOGY & HEPATOLOGY
卷 16, 期 2, 页码 121-136出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/s41575-018-0075-9
关键词
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资金
- Spanish Ministry of Economy and Competitiveness - Fondo Europeo de Desarrollo Regional (FEDER) [FIS PI12/00380, FIS PI15/01132, CON14/00129, FIS PI14/00399, PI17/00022, RYC-2015-17755, FIS PI16/00598, SAF2016-75197-R]
- ISCIII (CIBERehd), Spain
- Diputacion Foral Gipuzkoa [DFG15/010, DFG16/004]
- Fundacion Cientifica de la Asociacion Espanola Contra el Cancer (AECC Scientific Foundation)
- Department of Health of the Basque Country [2015111100]
- Basque Government [PRE_2016_1_0152, PRE_2016_1_0269]
- University of the Basque Country [UPV/EHU: PIF2014/11]
The canonical Wnt-beta-catenin pathway is a complex, evolutionarily conserved signalling mechanism that regulates fundamental physiological and pathological processes. Wnt-beta-catenin signalling tightly controls embryogenesis, including hepatobiliary development, maturation and zonation. In the mature healthy liver, the Wnt-beta-catenin pathway is mostly inactive but can become re-activated during cell renewal and/or regenerative processes, as well as in certain pathological conditions, diseases, pre-malignant conditions and cancer. In hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA), the two most prevalent primary liver tumours in adults, Wnt-beta-catenin signalling is frequently hyperactivated and promotes tumour growth and dissemination. A substantial proportion of liver tumours (mainly HCC and, to a lesser extent, CCA) have mutations in genes encoding key components of the Wnt-beta-catenin signalling pathway. Likewise, hepatoblastoma, the most common paediatric liver cancer, is characterized by Wnt-beta-catenin activation, mostly as a result of beta-catenin mutations. In this Review, we discuss the most relevant molecular mechanisms of action and regulation of Wnt-beta-catenin signalling in liver development and pathophysiology. Moreover, we highlight important preclinical and clinical studies and future directions in basic and clinical research.
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