Modulating β-catenin homeostasis for cancer therapy.

Abstract

β-Catenin is a well-established driver of many cancers; however, there are challenges in developing agents targeting β-catenin for clinical use. Recent progress has indicated that most of the pathological changes in β-catenin may be commonly caused by loss of protein homeostasis. Modulation of β-catenin homeostasis, especially by hyperactivation of β-catenin, potentially leads to robust antitumor outcomes. Here, we comprehensively dissect the protein homeostasis of β-catenin in terms of time, compartmentalization, supramolecular assemblies, and dynamics, with emphasis on changes in β-catenin homeostasis upon oncogenic mutations. We propose that altered β-catenin homeostasis could be deleterious for β-catenin-dependent cancers and that modulation of β-catenin homeostasis offers a novel avenue for targeting β-catenin for cancer therapy.