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 chemother apy 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...

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Detalhes bibliográficos
Autores: Jiménez Guerrero, Rocío, Belmonte-Fernández, Alejandro, Flores, M. Luz, González-Moreno, Mónica, Romero Portillo, Francisco, Saez, Carmen
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2021
País:España
Recursos:Universidad de Sevilla (US)
Repositorio:idUS. Depósito de Investigación de la Universidad de Sevilla
OAI Identifier:oai:idus.us.es:11441/131035
Acesso em linha:https://hdl.handle.net/11441/131035
https://doi.org/10.3390/ijms23010450
Access Level:acceso abierto
Palavra-chave:Wnt/β-catenin pathway
CSC phenotype
Paclitaxel resistance
Bladder cancer
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oai_identifier_str oai:idus.us.es:11441/131035
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spelling 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 Romero Portillo, Francisco Saez, Carmen Wnt/β-catenin pathway CSC phenotype Paclitaxel resistance Bladder cancer The Wnt/β-catenin pathway plays an important role in tumor progression and chemother apy 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. Instituto de Salud Carlos III FIS-PI17/1240 Instituto de Salud Carlos III FIS-PI20/1641 Ministry of Economy, Industry and Competitiveness SAF2017-87358-C2-1-R and -2-R Ministerio de Ciencia e Innovación PID2020-118774RB-C21 and -C22 Consejería de Salud y Familias PI-0213-2020 Consejería de Salud y Familias OH-0017-2018 MDPI https://hdl.handle.net/11441/131035 https://doi.org/10.3390/ijms23010450
title Wnt/β-Catenin Signaling Contributes to Paclitaxel Resistance in Bladder Cancer Cells with Cancer Stem Cell-Like Properties
spellingShingle Wnt/β-Catenin Signaling Contributes to Paclitaxel Resistance in Bladder Cancer Cells with Cancer Stem Cell-Like Properties
Jiménez Guerrero, Rocío
Wnt/β-catenin pathway
CSC phenotype
Paclitaxel resistance
Bladder cancer
title_short 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_sort Wnt/β-Catenin Signaling Contributes to Paclitaxel Resistance in Bladder Cancer Cells with Cancer Stem Cell-Like Properties
author Jiménez Guerrero, Rocío
author_facet Jiménez Guerrero, Rocío
Belmonte-Fernández, Alejandro
Flores, M. Luz
González-Moreno, Mónica
Romero Portillo, Francisco
Saez, Carmen
author_role author
author2 Belmonte-Fernández, Alejandro
Flores, M. Luz
González-Moreno, Mónica
Romero Portillo, Francisco
Saez, Carmen
author2_role author
author
author
author
author
topic Wnt/β-catenin pathway
CSC phenotype
Paclitaxel resistance
Bladder cancer
topic_facet Wnt/β-catenin pathway
CSC phenotype
Paclitaxel resistance
Bladder cancer
description The Wnt/β-catenin pathway plays an important role in tumor progression and chemother apy 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.
publishDate 2021
format article
status_str publishedVersion
url https://hdl.handle.net/11441/131035
https://doi.org/10.3390/ijms23010450
eu_rights_str_mv openAccess
publisher MDPI
institution Universidad de Sevilla (US)
collection idUS. Depósito de Investigación de la Universidad de Sevilla
reponame_str idUS. Depósito de Investigación de la Universidad de Sevilla
instname_str Universidad de Sevilla (US)
_version_ 1878442924743589889
publishDateSort 2021
author_browse Belmonte-Fernández, Alejandro
Flores, M. Luz
González-Moreno, Mónica
Jiménez Guerrero, Rocío
Romero Portillo, Francisco
Saez, Carmen
publisherStr MDPI
score 6,9303427

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