CD44v6 Drives Tumor Aggressiveness and Chemoresistance in Bladder Cancer
Iris LodewijkiD, Carolina RubioiD, Pontus ErikssoniD, Ignacio A. Reina, Esther Montesinos, Miguel Alonso-Sánchez, Laura García-Gómez, Álvaro Martín de BernardoiD, Lucía MoralesiD, Cristian Suárez-CabreraiD, Omaira AlberquillaiD, Rebeca Sánchez‐DomíngueziD, Félix Guerrero‐RamosiD, Rosa García-Martin, Lucía Parrilla, José Luis Rodríguez‐PeraltoiD, Daniel Castellano, Jesús María ParamioiD, Gottfrid SjödahliD, Marta DueñasiD
Abstract
Bladder cancer is a fast-moving and recurrent malignancy where survival hinges on early detection and precise risk stratification. The search for robust biomarkers is urgent, and CD44v6 has emerged as a compelling candidate. In this study, we reveal that CD44v6 is not merely a marker but a driver of urothelial carcinoma aggressiveness. Through integrated clinical and functional analyses, we show that high CD44v6 expression is strongly associated with poor patient outcomes. Mechanistic investigations demonstrate that CD44v6 amplifies the proliferative, migratory, and invasive potential of bladder cancer cells, while conferring marked resistance to cisplatin. These findings position CD44v6 at the intersection of tumor progression and therapeutic failure, underscoring its value as both a prognostic biomarker and a promising therapeutic target. Targeting CD44v6 could pave the way for strategies that curb disease aggressiveness and overcome chemoresistance in bladder cancer.
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