Epigenetic Activation of Wnt/ß-Catenin Signaling in NAFLD-Associated Hepatocarcinogenesis.
Cancers (Basel)
; 8(8)2016 Aug 20.
Article
em En
| MEDLINE
| ID: mdl-27556491
ABSTRACT
Non-alcoholic fatty liver disease (NAFLD), characterized by fat accumulation in liver, is closely associated with central obesity, over-nutrition and other features of metabolic syndrome, which elevate the risk of developing hepatocellular carcinoma (HCC). The Wnt/ß-catenin signaling pathway plays a significant role in the physiology and pathology of liver. Up to half of HCC patients have activation of Wnt/ß-catenin signaling. However, the mutation frequencies of CTNNB1 (encoding ß-catenin protein) or other antagonists targeting Wnt/ß-catenin signaling are low in HCC patients, suggesting that genetic mutations are not the major factor driving abnormal ß-catenin activities in HCC. Emerging evidence has demonstrated that obesity-induced metabolic pathways can deregulate chromatin modifiers such as histone deacetylase 8 to trigger undesired global epigenetic changes, thereby modifying gene expression program which contributes to oncogenic signaling. This review focuses on the aberrant epigenetic activation of Wnt/ß-catenin in the development of NAFLD-associated HCC. A deeper understanding of the molecular mechanisms underlying such deregulation may shed light on the identification of novel druggable epigenetic targets for the prevention and/or treatment of HCC in obese and diabetic patients.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Idioma:
En
Revista:
Cancers (Basel)
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
China