Integrin beta 4 promotes colorectal cancer progression by upregulating Ezrin and activating the Wnt/β-catenin signaling pathway

Similarly, silencing ITGB4 markedly inhibited tumor growth in the in vivo xenograft model. RNA-seq analysis identified Ezrin (EZR) as a key downstream target of ITGB4, and a direct protein-protein interaction was confirmed between them. Mechanistically, ITGB4 knockdown decreased the expression of EZR at both the mRNA and protein levels.

ITGB4 was demonstrated to exert its pro-tumorigenic effects through the regulation of EZR, which subsequently activated the Wnt/β-catenin signaling pathway. Interestingly, EZR overexpression partially restored ITGB4 levels, suggesting a potential positive feedback loop via Wnt/β-catenin signaling that further amplifies this oncogenic axis. Notably, the malignant phenotypes suppressed by ITGB4 silencing were significantly rescued by the overexpression of EZR.The present study identified a novel ITGB4/EZR/Wnt/β-catenin signaling axis in colorectal cancer.

ITGB4 promotes CRC progression by modulating EZR expression and subsequently activating the Wnt/β-catenin pathway. These findings highlight ITGB4 as a potential prognostic biomarker and a promising therapeutic target for CRC.