Related Experiment Video For Hopx+ ISCs
Updated: May 21, 2026

Reconstitution Of β-catenin Degradation In Xenopus Egg Extract
Published on: June 17, 2014
Competitive Binding of UBA52 and HOPX Modulates β-catenin Stability in Colorectal Cancer in the Context of High-Iron
Xiangjun Liu1, Tong Tang1, Xi Wang1
1Precision Radiation in Oncology Key Laboratory of Sichuan Province, Sichuan Cancer Hospital & Institute, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610041, China.
Abstract:
Over-intake of dietary iron and hereditary iron overload are implicated in colorectal cancer (CRC) carcinogenesis, yet the mechanistic basis of how iron-mediated signaling leads to oncogenesis remains enigmatic. Here we demonstrate that high iron diet augments the regenerative capacity of Hopx+ intestinal stem cells (ISCs) rather than Lgr5+ ISCs to functionally contribute to colon tumor formation. Mechanistically, high iron activates a robust Wnt/β-catenin signaling in ISCs to enhance the proliferation of colonic cells in a Hopx-dependent manner. Furthermore, Wnt/β-catenin induction is attributed to Hopx stabilizing β-catenin protein by directly inhibiting the interaction of β-catenin with UBA52, which targets ubiquitination degradation of β-catenin. This study thus identifies an iron-triggered pathway regulating intestinal tumorigenesis and indicates that iron interventions may complement current prevention and treatment strategies for CRC, and Hopx is a previously unrecognized regulator of β-catenin and a therapeutic target of CRC.
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