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Wnt/β-Catenin Signaling Contributes to Paclitaxel Resistance in Bladder Cancer Cells with Cancer Stem Cell-Like Properties

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 w...

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Autores principales: Jiménez-Guerrero, Rocío, Belmonte-Fernández, Alejandro, Flores, M. Luz, González-Moreno, Mónica, Pérez-Valderrama, Begoña, Romero, Francisco, Japón, Miguel Á., Sáez, Carmen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8745426/
https://www.ncbi.nlm.nih.gov/pubmed/35008872
http://dx.doi.org/10.3390/ijms23010450
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author Jiménez-Guerrero, Rocío
Belmonte-Fernández, Alejandro
Flores, M. Luz
González-Moreno, Mónica
Pérez-Valderrama, Begoña
Romero, Francisco
Japón, Miguel Á.
Sáez, Carmen
author_facet Jiménez-Guerrero, Rocío
Belmonte-Fernández, Alejandro
Flores, M. Luz
González-Moreno, Mónica
Pérez-Valderrama, Begoña
Romero, Francisco
Japón, Miguel Á.
Sáez, Carmen
author_sort Jiménez-Guerrero, Rocío
collection PubMed
description 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.
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spelling pubmed-87454262022-01-11 Wnt/β-Catenin Signaling Contributes to Paclitaxel Resistance in Bladder Cancer Cells with Cancer Stem Cell-Like Properties Jiménez-Guerrero, Rocío Belmonte-Fernández, Alejandro Flores, M. Luz González-Moreno, Mónica Pérez-Valderrama, Begoña Romero, Francisco Japón, Miguel Á. Sáez, Carmen Int J Mol Sci Article 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. MDPI 2021-12-31 /pmc/articles/PMC8745426/ /pubmed/35008872 http://dx.doi.org/10.3390/ijms23010450 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Jiménez-Guerrero, Rocío
Belmonte-Fernández, Alejandro
Flores, M. Luz
González-Moreno, Mónica
Pérez-Valderrama, Begoña
Romero, Francisco
Japón, Miguel Á.
Sáez, Carmen
Wnt/β-Catenin Signaling Contributes to Paclitaxel Resistance in Bladder Cancer Cells with Cancer Stem Cell-Like Properties
title Wnt/β-Catenin Signaling Contributes to Paclitaxel Resistance in Bladder Cancer Cells with Cancer Stem Cell-Like Properties
title_full Wnt/β-Catenin Signaling Contributes to Paclitaxel Resistance in Bladder Cancer Cells with Cancer Stem Cell-Like Properties
title_fullStr Wnt/β-Catenin Signaling Contributes to Paclitaxel Resistance in Bladder Cancer Cells with Cancer Stem Cell-Like Properties
title_full_unstemmed Wnt/β-Catenin Signaling Contributes to Paclitaxel Resistance in Bladder Cancer Cells with Cancer Stem Cell-Like Properties
title_short Wnt/β-Catenin Signaling Contributes to Paclitaxel Resistance in Bladder Cancer Cells with Cancer Stem Cell-Like Properties
title_sort wnt/β-catenin signaling contributes to paclitaxel resistance in bladder cancer cells with cancer stem cell-like properties
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8745426/
https://www.ncbi.nlm.nih.gov/pubmed/35008872
http://dx.doi.org/10.3390/ijms23010450
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