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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Authors: Jiménez Guerrero, Rocío, Belmonte-Fernández, Alejandro, Flores, M. Luz, González-Moreno, Mónica, Romero Portillo, Francisco, Saez, Carmen
Format: article
Status:Published version
Publication Date:2021
Country:España
Institution:Universidad de Sevilla (US)
Repository:idUS. Depósito de Investigación de la Universidad de Sevilla
OAI Identifier:oai:idus.us.es:11441/131035
Online Access:https://hdl.handle.net/11441/131035
https://doi.org/10.3390/ijms23010450
Access Level:Open access
Keyword:Wnt/β-catenin pathway
CSC phenotype
Paclitaxel resistance
Bladder cancer
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spelling Wnt/β-Catenin Signaling Contributes to Paclitaxel Resistance in Bladder Cancer Cells with Cancer Stem Cell-Like PropertiesJiménez Guerrero, RocíoBelmonte-Fernández, AlejandroFlores, M. LuzGonzález-Moreno, MónicaRomero Portillo, FranciscoSaez, CarmenWnt/β-catenin pathwayCSC phenotypePaclitaxel resistanceBladder cancerThe 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-PI17/1240Instituto de Salud Carlos III FIS-PI20/1641Ministry of Economy, Industry and Competitiveness SAF2017-87358-C2-1-R and -2-RMinisterio de Ciencia e Innovación PID2020-118774RB-C21 and -C22Consejería de Salud y Familias PI-0213-2020Consejería de Salud y Familias OH-0017-2018MDPIMicrobiología2021info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/11441/131035https://doi.org/10.3390/ijms23010450reponame:idUS. Depósito de Investigación de la Universidad de Sevillainstname:Universidad de Sevilla (US)InglésInternational Journal of Molecular Sciences, 23 (1)https://www.mdpi.com/1422-0067/23/1/450info:eu-repo/semantics/openAccessoai:idus.us.es:11441/1310352026-06-17T12:51:07Z
dc.title.none.fl_str_mv 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
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
dc.creator.none.fl_str_mv Jiménez Guerrero, Rocío
Belmonte-Fernández, Alejandro
Flores, M. Luz
González-Moreno, Mónica
Romero Portillo, Francisco
Saez, Carmen
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
dc.contributor.none.fl_str_mv Microbiología
dc.subject.none.fl_str_mv Wnt/β-catenin pathway
CSC phenotype
Paclitaxel resistance
Bladder cancer
topic 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
dc.date.none.fl_str_mv 2021
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/11441/131035
https://doi.org/10.3390/ijms23010450
url https://hdl.handle.net/11441/131035
https://doi.org/10.3390/ijms23010450
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv International Journal of Molecular Sciences, 23 (1)
https://www.mdpi.com/1422-0067/23/1/450
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv reponame:idUS. Depósito de Investigación de la Universidad de Sevilla
instname:Universidad de Sevilla (US)
instname_str Universidad de Sevilla (US)
reponame_str idUS. Depósito de Investigación de la Universidad de Sevilla
collection idUS. Depósito de Investigación de la Universidad de Sevilla
repository.name.fl_str_mv
repository.mail.fl_str_mv
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