Role of the microtubule-targeting drug vinflunine on cell-cell adhesions in bladder epithelial tumour cells

Background: Vinflunine (VFL) is a microtubule-targeting drug that suppresses microtubule dynamics, showing anti-metastatic properties both in vitro and in living cancer cells. An increasing body of evidence underlines the influence of the microtubules dynamics on the cadherin-dependent cell-cell adh...

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Autores: Antón Aparicio, Luis Miguel, Castosa, R, Haz Conde, María del Mar, Rodríguez, M, Blanco Calvo, Moisés, Valladares Ayerbes, Manuel, Figueroa Conde-Valvís, Angélica
Tipo de recurso: artículo
Fecha de publicación:2014
País:España
Institución:Servizo Galego de Saúde (SERGAS)
Repositorio:RUNA. Repositorio da Consellería de Sanidade e Sergas
OAI Identifier:oai:runa.sergas.gal:20.500.11940/8022
Acceso en línea:http://hdl.handle.net/20.500.11940/8022
Access Level:acceso abierto
Palabra clave:Microtubules
Vinblastine
Urinary Bladder Neoplasms
Cell Adhesion
Apoptosis
Microtúbulos
Vinblastina
Neoplasias de la Vejiga Urinaria
Adhesión Celular
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spelling Role of the microtubule-targeting drug vinflunine on cell-cell adhesions in bladder epithelial tumour cellsAntón Aparicio, Luis MiguelCastosa, RHaz Conde, María del MarRodríguez, MBlanco Calvo, MoisésValladares Ayerbes, ManuelFigueroa Conde-Valvís, AngélicaMicrotubulesVinblastineUrinary Bladder NeoplasmsCell AdhesionApoptosisMicrotúbulosVinblastinaNeoplasias de la Vejiga UrinariaAdhesión CelularApoptosisBackground: Vinflunine (VFL) is a microtubule-targeting drug that suppresses microtubule dynamics, showing anti-metastatic properties both in vitro and in living cancer cells. An increasing body of evidence underlines the influence of the microtubules dynamics on the cadherin-dependent cell-cell adhesions. E-cadherin is a marker of epithelial-to-mesenchymal transition (EMT) and a tumour suppressor; its reduced levels in carcinoma are associated with poor prognosis. In this report, we investigate the role of VFL on cell-cell adhesions in bladder epithelial tumour cells. Methods: Human bladder epithelial tumour cell lines HT1376, 5637, SW780, T24 and UMUC3 were used to analyse cadherin-dependent cell-cell adhesions under VFL treatment. VFL effect on growth inhibition was measured by using a MTT colorimetric cell viability assay. Western blot, immunofluorescence and transmission electron microscopy analyses were performed to assess the roles of VFL effect on cell-cell adhesions, epithelial-to-mesenchymal markers and apoptosis. The role of the proteasome in controlling cell-cell adhesion was studied using the proteasome inhibitor MG132. Results: We show that VFL induces cell death in bladder cancer cells and activates epithelial differentiation of the remaining living cells, leading to an increase of E-cadherin-dependent cell-cell adhesion and a reduction of mesenchymal markers, such as N-cadherin or vimentin. Moreover, while E-cadherin is increased, the levels of Hakai, an E3 ubiquitin-ligase for E-cadherin, were significantly reduced in presence of VFL. In 5637, this reduction on Hakai expression was blocked by MG132 proteasome inhibitor, indicating that the proteasome pathway could be one of the molecular mechanisms involved in its degradation. Conclusions: Our findings underscore a critical function for VFL in cell-cell adhesions of epithelial bladder tumour cells, suggesting a novel molecular mechanism by which VFL may impact upon EMT and metastasis.2014info:eu-repo/semantics/articlehttp://hdl.handle.net/20.500.11940/8022reponame:RUNA. Repositorio da Consellería de Sanidade e Sergasinstname:Servizo Galego de Saúde (SERGAS)Ingléshttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:runa.sergas.gal:20.500.11940/80222026-06-12T08:40:47Z
dc.title.none.fl_str_mv Role of the microtubule-targeting drug vinflunine on cell-cell adhesions in bladder epithelial tumour cells
title Role of the microtubule-targeting drug vinflunine on cell-cell adhesions in bladder epithelial tumour cells
spellingShingle Role of the microtubule-targeting drug vinflunine on cell-cell adhesions in bladder epithelial tumour cells
Antón Aparicio, Luis Miguel
Microtubules
Vinblastine
Urinary Bladder Neoplasms
Cell Adhesion
Apoptosis
Microtúbulos
Vinblastina
Neoplasias de la Vejiga Urinaria
Adhesión Celular
Apoptosis
title_short Role of the microtubule-targeting drug vinflunine on cell-cell adhesions in bladder epithelial tumour cells
title_full Role of the microtubule-targeting drug vinflunine on cell-cell adhesions in bladder epithelial tumour cells
title_fullStr Role of the microtubule-targeting drug vinflunine on cell-cell adhesions in bladder epithelial tumour cells
title_full_unstemmed Role of the microtubule-targeting drug vinflunine on cell-cell adhesions in bladder epithelial tumour cells
title_sort Role of the microtubule-targeting drug vinflunine on cell-cell adhesions in bladder epithelial tumour cells
dc.creator.none.fl_str_mv Antón Aparicio, Luis Miguel
Castosa, R
Haz Conde, María del Mar
Rodríguez, M
Blanco Calvo, Moisés
Valladares Ayerbes, Manuel
Figueroa Conde-Valvís, Angélica
author Antón Aparicio, Luis Miguel
author_facet Antón Aparicio, Luis Miguel
Castosa, R
Haz Conde, María del Mar
Rodríguez, M
Blanco Calvo, Moisés
Valladares Ayerbes, Manuel
Figueroa Conde-Valvís, Angélica
author_role author
author2 Castosa, R
Haz Conde, María del Mar
Rodríguez, M
Blanco Calvo, Moisés
Valladares Ayerbes, Manuel
Figueroa Conde-Valvís, Angélica
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv Microtubules
Vinblastine
Urinary Bladder Neoplasms
Cell Adhesion
Apoptosis
Microtúbulos
Vinblastina
Neoplasias de la Vejiga Urinaria
Adhesión Celular
Apoptosis
topic Microtubules
Vinblastine
Urinary Bladder Neoplasms
Cell Adhesion
Apoptosis
Microtúbulos
Vinblastina
Neoplasias de la Vejiga Urinaria
Adhesión Celular
Apoptosis
description Background: Vinflunine (VFL) is a microtubule-targeting drug that suppresses microtubule dynamics, showing anti-metastatic properties both in vitro and in living cancer cells. An increasing body of evidence underlines the influence of the microtubules dynamics on the cadherin-dependent cell-cell adhesions. E-cadherin is a marker of epithelial-to-mesenchymal transition (EMT) and a tumour suppressor; its reduced levels in carcinoma are associated with poor prognosis. In this report, we investigate the role of VFL on cell-cell adhesions in bladder epithelial tumour cells. Methods: Human bladder epithelial tumour cell lines HT1376, 5637, SW780, T24 and UMUC3 were used to analyse cadherin-dependent cell-cell adhesions under VFL treatment. VFL effect on growth inhibition was measured by using a MTT colorimetric cell viability assay. Western blot, immunofluorescence and transmission electron microscopy analyses were performed to assess the roles of VFL effect on cell-cell adhesions, epithelial-to-mesenchymal markers and apoptosis. The role of the proteasome in controlling cell-cell adhesion was studied using the proteasome inhibitor MG132. Results: We show that VFL induces cell death in bladder cancer cells and activates epithelial differentiation of the remaining living cells, leading to an increase of E-cadherin-dependent cell-cell adhesion and a reduction of mesenchymal markers, such as N-cadherin or vimentin. Moreover, while E-cadherin is increased, the levels of Hakai, an E3 ubiquitin-ligase for E-cadherin, were significantly reduced in presence of VFL. In 5637, this reduction on Hakai expression was blocked by MG132 proteasome inhibitor, indicating that the proteasome pathway could be one of the molecular mechanisms involved in its degradation. Conclusions: Our findings underscore a critical function for VFL in cell-cell adhesions of epithelial bladder tumour cells, suggesting a novel molecular mechanism by which VFL may impact upon EMT and metastasis.
publishDate 2014
dc.date.none.fl_str_mv 2014
dc.type.none.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/20.500.11940/8022
url http://hdl.handle.net/20.500.11940/8022
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv http://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.source.none.fl_str_mv reponame:RUNA. Repositorio da Consellería de Sanidade e Sergas
instname:Servizo Galego de Saúde (SERGAS)
instname_str Servizo Galego de Saúde (SERGAS)
reponame_str RUNA. Repositorio da Consellería de Sanidade e Sergas
collection RUNA. Repositorio da Consellería de Sanidade e Sergas
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.300719

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