title: CUL4B: a novel epigenetic driver in Wnt/β-catenin-dependent hepatocarcinogenesis.
abstract: Emerging evidence indicates that Cullin 4B (CUL4B), a major component of ubiquitin ligase complexes, is over-expressed in diverse cancer types with pro-tumourigenic effects. In this issue of the Journal of Pathology, Yuan and colleagues [6] elucidated the oncogenic activity of CUL4B in hepatocellular carcinoma (HCC) and delineated its role in driving Wnt/β-catenin signalling. In addition to the stabilization of β-catenin protein against proteasomal degradation, CUL4B also acts in concert with enhancer of Zeste homologue 2 (EZH2) to concordantly silence multiple Wnt inhibitors. These findings provide significant mechanistic insights into the epigenetic activation of the Wnt/β-catenin pathway in HCC and shed light on the functional importance of ubiquitination in this intricate regulatory system.
authors: School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong SAR, China; Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen, China.
authors: Myth T S
authors: MT
authors: Mok
authors: Alfred S L
authors: AS
authors: Cheng
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000201:enzymology*; D044842:Cullin Proteins / Q000378:metabolism*; D006801:Humans; D008113:Liver Neoplasms / Q000201:enzymology*; D060449:Wnt Signaling Pathway; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D044842:Cullin Proteins; D051176:beta Catenin
keywords: CUL4B; EZH2; Wnt antagonists; hepatocellular carcinoma; ubiquitination; β-catenin