CUL4B : a novel epigenetic driver in Wnt/β‐catenin‐dependent hepatocarcinogenesis

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. Copyright © 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.