Role of MED15 in Enhancing EMT and Metastasis in Bladder Cancer Through YAP1 Stabilization

Bladder cancer (BLCA) remains a highly prevalent and aggressive malignancy of the urinary tract, characterized by frequent recurrence and metastasis. Mediator complex subunit 15 (MED15) functions as a key transcriptional coactivator bridging transcription factors and RNA polymerase II, yet its role in BLCA progression has not been elucidated. Here, we identify MED15 as markedly upregulated in BLCA tissues. Gene set enrichment analysis (GSEA) revealed that MED15 expression correlates with epithelial-mesenchymal transition (EMT)-related pathways. Functionally, loss- and gain-of-function assays demonstrated that MED15 promotes EMT and enhances cell migration in a YAP1-dependent manner. Mechanistically, MED15 interacts with YAP1 and stabilizes it by attenuating TRIM11-mediated ubiquitination. Furthermore, under sorbitol-induced stress conditions-mimicking selected features of the bladder urothelium-MED15 forms stress-inducible, protein condensates and exhibits increased colocalization with YAP1. Collectively, these findings uncover a previously unrecognized MED15-TRIM11-YAP1 regulatory axis and support a model in which stress-induced MED15 condensates are associated with YAP1 stabilization and pro-metastatic behavior in bladder cancer.