Role of Ubiquitin-regulated EMT in Cancer Metastasis and Chemoresistance
Shuai Xiao, Lingli Tian, Xiaoli Gan, Xiaozhen Xu, Meng Liao, Dandan Song, Yeping Yu, Wenying Qin, Rui Zhang, Hui Lyu, Dong Guo, Qi Zhang, Xing-Zhen Chen, Cefan Zhou, Jingfeng Tang
Abstract
Epithelial-mesenchymal transition (EMT) is a fundamental biological process that promotes cancer metastasis and chemoresistance. However, the therapeutic efficacy of EMT inhibitors remains limited. Ubiquitination, a critical post-translational modification, involves attaching ubiquitin molecules to proteins to regulate their function and stability. It modulates EMT by controlling key EMT transcription factors (EMT-TFs) and associated signaling pathways. Evidence indicates that ubiquitination-dependent regulation of EMT serves as a central mechanism underlying tumor metastasis and chemoresistance. Targeting specific deubiquitinases (DUBs) or E3 ligases can effectively reverse EMT-induced cancer progression and treatment resistance. These findings highlight the therapeutic potential of E3 ligase and DUB inhibitors in oncology. Collectively, ubiquitination-regulated EMT is pivotal in mediating metastasis and chemoresistance in malignant tumors. This review summarizes the molecular mechanisms of EMT and emphasizes ubiquitination's essential role in regulating EMT to promote tumor metastasis and chemoresistance. Consequently, developing inhibitors against specific E3 ligases and DUBs offers a promising strategy to improve cancer treatment outcomes.