mTOR-Dependent ARID1A Degradation: A New Twist in the Genetic-Epigenetic Interplay Driving Hepatocellular Carcinoma.

The importance of the cross-talk between the genetic and epigenetic alterations promoting cancer development is well understood; however, the molecular details underlying the mechanism of how oncogenic signaling remodels the epigenome to generate a procancer transcriptome require further elucidation. The study by Zhang and colleagues in this issue of Cancer Research reveals a novel role for oncogenic mTOR signaling leading to the degradation of a prominent chromatin remodeler, ARID1a, establishing an altered, protumor chromatin landscape in hepatocellular carcinoma (HCC) controlling tumor deve-lopment and treatment resistance. These findings highlight oncogenic effects on chromatin remodelers as an important factor in both HCC pathobiology and therapeutic response. As strategies for cancer therapy begin to move in an increasingly individualized direction, increased knowledge into the impact of restoring the function of chromatin remodelers on response to therapy is warranted. See related article by Zhang et al., p. 5652 .
(©2021 American Association for Cancer Research.)