RT Journal Article
T1 Wnt/β-Catenin Signaling Contributes to Paclitaxel Resistance in Bladder Cancer Cells with Cancer Stem Cell-Like Properties.
A1 Jiménez-Guerrero, Rocío
A1 Belmonte-Fernández, Alejandro
A1 Flores, M Luz
A1 González-Moreno, Mónica
A1 Pérez-Valderrama, Begoña
A1 Romero, Francisco
A1 Japón, Miguel Á
A1 Sáez, Carmen
K1 CSC phenotype
K1 Wnt/β-catenin pathway
K1 bladder cancer
K1 paclitaxel resistance
AB The Wnt/β-catenin pathway plays an important role in tumor progression and chemotherapy resistance and seems to be essential for the maintenance of cancer stem cells (CSC) in several tumor types. However, the interplay of these factors has not been fully addressed in bladder cancer. Here, our goal was to analyze the role of the Wnt/β-catenin pathway in paclitaxel resistance and to study the therapeutic efficacy of its inhibition in bladder cancer cells, as well as to determine its influence in the maintenance of the CSC-like phenotype in bladder cancer. Our results show that paclitaxel-resistant HT1197 cells have hyperactivation of the Wnt/β-catenin pathway and increased CSC-like properties compared with paclitaxel-sensitive 5637 cells. Paclitaxel sensitivity diminishes in 5637 cells after β-catenin overexpression or when they are grown as tumorspheres, enriched for the CSC-like phenotype. Additionally, downregulation of β-catenin or inhibition with XAV939 sensitizes HT1197 cells to paclitaxel. Moreover, a subset of muscle-invasive bladder carcinomas shows aberrant expression of β-catenin that associates with positive expression of the CSC marker ALDH1A1. In conclusion, we demonstrate that Wnt/β-catenin signaling contributes to paclitaxel resistance in bladder cancer cells with CSC-like properties.
YR 2021
FD 2021-12-31
LK http://hdl.handle.net/10668/21131
UL http://hdl.handle.net/10668/21131
LA en
DS RISalud
RD Apr 10, 2025