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/-catenin signalling. In addition to the stabilization of -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/-catenin pathway in HCC and shed light on the functional importance of ubiquitination in this intricate regulatory system. Copyright (c) 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.