Notch-mediated induction of N-cadherin and a9-integrin confers higher invasive phenotype on rhabdomyosarcoma cells

BACKGROUND: Rhabdomyosarcoma (RMS) is the commonest type of soft-tissue sarcoma in children. Patients with metastatic RMS continue to have very poor prognosis. Recently, several works have demonstrated a connection between Notch pathway activation and the regulation of cell motility and invasiveness...

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Autores: Masià, A, Almazán-Moga, A, Velasco, P, Reventós, J, Torán, N, de Toledo, JS, Roma, J, Gallego, S
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2012
País:España
Institución:Fundació Sant Joan de Déu
Repositorio:r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu
OAI Identifier:oai:fsjd.fundanetsuite.com:p28198
Acceso en línea:https://fsjd.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=28198
Access Level:acceso abierto
Palabra clave:rhabdomyosarcoma
Notch
NCAD
ITGA9
invasion
soft-tissue sarcomas
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spelling Notch-mediated induction of N-cadherin and a9-integrin confers higher invasive phenotype on rhabdomyosarcoma cellsMasià, AAlmazán-Moga, AVelasco, PReventós, JTorán, Nde Toledo, JSRoma, JGallego, SrhabdomyosarcomaNotchNCADITGA9invasionsoft-tissue sarcomasBACKGROUND: Rhabdomyosarcoma (RMS) is the commonest type of soft-tissue sarcoma in children. Patients with metastatic RMS continue to have very poor prognosis. Recently, several works have demonstrated a connection between Notch pathway activation and the regulation of cell motility and invasiveness. However, the molecular mechanisms of this possible relationship remain unclear. METHODS: The Notch pathway was manipulated pharmacologically and genetically. The mRNA changes were analysed by quantitative PCR and protein variations by western blot and immunofluorescence. Finally, the capabilities of RMS cells to adhere, heal a wound and invade were assessed in the presence of neuronal cadherin (N-cadherin)- and alpha 9-integrin-blocking antibodies. RESULTS: Cells treated with gamma-secretase inhibitor showed lower adhesion capability and downregulation of N-cadherin and alpha 9-integrin. Genetic manipulation of the Notch pathway led to concomitant variations in N-cadherin and alpha 9-integrin. Treatment with anti-N-cadherin-blocking antibody rendered marked inhibition of cell adhesion and motility, while anti-alpha 9-integrin-blocking antibody exerted a remarkable effect on cell adhesion and invasiveness. CONCLUSION: Neuronal cadherin and alpha 9-integrin are postulated as leading actors in the association between the Notch pathway and promotion of cell adhesion, motility and invasion, pointing to these proteins and the Notch pathway itself as interesting putative targets for new molecular therapies against metastases in RMS. British Journal of Cancer (2012) 107, 1374-1383. doi:10.1038/bjc.2012.411 www.bjcancer.com Published online 13 September 2012 (C) 2012 Cancer Research UKSPRINGERNATURE2012info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://fsjd.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=28198BRITISH JOURNAL OF CANCERISSN: 00070920ISSNe: 15321827reponame:r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déuinstname:Fundació Sant Joan de DéuInglésinfo:eu-repo/semantics/openAccessoai:fsjd.fundanetsuite.com:p281982026-05-27T12:37:41Z
dc.title.none.fl_str_mv Notch-mediated induction of N-cadherin and a9-integrin confers higher invasive phenotype on rhabdomyosarcoma cells
title Notch-mediated induction of N-cadherin and a9-integrin confers higher invasive phenotype on rhabdomyosarcoma cells
spellingShingle Notch-mediated induction of N-cadherin and a9-integrin confers higher invasive phenotype on rhabdomyosarcoma cells
Masià, A
rhabdomyosarcoma
Notch
NCAD
ITGA9
invasion
soft-tissue sarcomas
title_short Notch-mediated induction of N-cadherin and a9-integrin confers higher invasive phenotype on rhabdomyosarcoma cells
title_full Notch-mediated induction of N-cadherin and a9-integrin confers higher invasive phenotype on rhabdomyosarcoma cells
title_fullStr Notch-mediated induction of N-cadherin and a9-integrin confers higher invasive phenotype on rhabdomyosarcoma cells
title_full_unstemmed Notch-mediated induction of N-cadherin and a9-integrin confers higher invasive phenotype on rhabdomyosarcoma cells
title_sort Notch-mediated induction of N-cadherin and a9-integrin confers higher invasive phenotype on rhabdomyosarcoma cells
dc.creator.none.fl_str_mv Masià, A
Almazán-Moga, A
Velasco, P
Reventós, J
Torán, N
de Toledo, JS
Roma, J
Gallego, S
author Masià, A
author_facet Masià, A
Almazán-Moga, A
Velasco, P
Reventós, J
Torán, N
de Toledo, JS
Roma, J
Gallego, S
author_role author
author2 Almazán-Moga, A
Velasco, P
Reventós, J
Torán, N
de Toledo, JS
Roma, J
Gallego, S
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv rhabdomyosarcoma
Notch
NCAD
ITGA9
invasion
soft-tissue sarcomas
topic rhabdomyosarcoma
Notch
NCAD
ITGA9
invasion
soft-tissue sarcomas
description BACKGROUND: Rhabdomyosarcoma (RMS) is the commonest type of soft-tissue sarcoma in children. Patients with metastatic RMS continue to have very poor prognosis. Recently, several works have demonstrated a connection between Notch pathway activation and the regulation of cell motility and invasiveness. However, the molecular mechanisms of this possible relationship remain unclear. METHODS: The Notch pathway was manipulated pharmacologically and genetically. The mRNA changes were analysed by quantitative PCR and protein variations by western blot and immunofluorescence. Finally, the capabilities of RMS cells to adhere, heal a wound and invade were assessed in the presence of neuronal cadherin (N-cadherin)- and alpha 9-integrin-blocking antibodies. RESULTS: Cells treated with gamma-secretase inhibitor showed lower adhesion capability and downregulation of N-cadherin and alpha 9-integrin. Genetic manipulation of the Notch pathway led to concomitant variations in N-cadherin and alpha 9-integrin. Treatment with anti-N-cadherin-blocking antibody rendered marked inhibition of cell adhesion and motility, while anti-alpha 9-integrin-blocking antibody exerted a remarkable effect on cell adhesion and invasiveness. CONCLUSION: Neuronal cadherin and alpha 9-integrin are postulated as leading actors in the association between the Notch pathway and promotion of cell adhesion, motility and invasion, pointing to these proteins and the Notch pathway itself as interesting putative targets for new molecular therapies against metastases in RMS. British Journal of Cancer (2012) 107, 1374-1383. doi:10.1038/bjc.2012.411 www.bjcancer.com Published online 13 September 2012 (C) 2012 Cancer Research UK
publishDate 2012
dc.date.none.fl_str_mv 2012
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://fsjd.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=28198
url https://fsjd.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=28198
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv SPRINGERNATURE
publisher.none.fl_str_mv SPRINGERNATURE
dc.source.none.fl_str_mv BRITISH JOURNAL OF CANCER
ISSN: 00070920
ISSNe: 15321827
reponame:r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu
instname:Fundació Sant Joan de Déu
instname_str Fundació Sant Joan de Déu
reponame_str r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu
collection r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu
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repository.mail.fl_str_mv
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