δ-catenin promotes Twist1 stabilization in prostate cancer through ubiquitination modification.

Abstract

Prostate cancer generally has a high long-term survival rate; however, metastatic prostate cancer remains largely incurable despite intensive multimodal therapy. Recent research has identified δ-catenin, a member of the catenin family, as playing a crucial role in the progression of prostate cancer. Nonetheless, the extent to which δ-catenin influences transcription factors associated with epithelial-mesenchymal transition (EMT) has not been thoroughly explored. This study aims to investigate the hypothesis that δ-catenin enhances the stability of Twist1, thereby promoting the migratory and invasive capabilities of prostate cancer cells. Clinical data indicate a strong correlation between δ-catenin and Twist1 expression levels. Western blot analysis confirmed that δ-catenin stabilizes Twist1 and induces ectopic expression. Additionally, δ-catenin was found to reduce Twist1 phosphorylation by inhibiting GSK-3β activity. Immunoprecipitation analysis suggested that δ-catenin exerts its effect by competing with Twist1 for binding to ubiquitin (Ub). These results highlight the role of δ-catenin in the ubiquitination modification of Twist1, suggesting that the combined presence of δ-catenin and Twist1 could serve as a biomarker for tumor progression in prostate cancer.