Exploring the role of YES1 kinase in regulating cisplatin resistance through iTRAQ-based quantitative proteomic analysis in urothelial carcinoma

Urothelial carcinoma (UC) is a highly metastatic cancer that frequently develops resistance to platinum-based chemotherapy, although the underlying mechanisms remain unclear. While certain genes have been implicated in UC drug resistance, their specific roles require further validation. In this study, we established a cisplatin-resistant UC cell line (BFTC909 Cis-R) and used iTRAQ analysis to compare differences in protein expression between BFTC909 Cis-R cells and their parental BFTC909 counterparts. iTRAQ mass analysis revealed decreased expression of the tyrosine kinase YES1 in BFTC909 Cis-R cells, along with reduced levels of YES1 and YAP in both BFTC909 Cis-R and T24 Cis-R cells. Moreover, we found that bladder cancer patients with higher YES1 expression had significantly better survival outcomes in our in-house cohort and two public datasets (GSE13507 and GSE169455). Treatment with dasatinib, a YES1 inhibitor, reduced cisplatin-induced cytotoxicity in UMUC-14 cells, suggesting that YES1 influences cisplatin efficacy in UC cells. Our findings indicate that YES1 plays a critical role in cisplatin resistance and may represent a promising therapeutic target in bladder cancer.