Extracellular cleavage and shedding of P-cadherin: a mechanism underlying the invasive behaviour of breast cancer cells
Autor(a) principal: | |
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Data de Publicação: | 2010 |
Outros Autores: | , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/1822/67565 |
Resumo: | Cell-cell adhesion is an elementary process in normal epithelial cellular architecture. Several studies have shown the role mediated by cadherins in this process, besides their role in the maintenance of cell polarity, differentiation and cell growth. However, during tumour progression, these molecules are frequently altered. In breast cancer, tumours that overexpress P-cadherin usually present a high histological grade, show decreased cell polarity and are associated with worse patient survival. However, little is known about how this protein dictates the very aggressive behaviour of these tumours. To achieve this goal, we set up two breast cancer cell models, where P-cadherin expression was differently modulated and analysed in terms of cell invasion, motility and migration. We show that P-cadherin overexpression, in breast cancer cells with wild-type E-cadherin, promotes cell invasion, motility and migration. Moreover, we found that the overexpression of P-cadherin induces the secretion of matrix metalloproteases, specifically MMP-1 and MMP-2, which then lead to P-cadherin ectodomain cleavage. Further, we showed that soluble P-cadherin fragment is able to induce in vitro invasion of breast cancer cells. Overall, our results contribute to elucidate the mechanism underlying the invasive behaviour of P-cadherin expressing breast tumours. |
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Extracellular cleavage and shedding of P-cadherin: a mechanism underlying the invasive behaviour of breast cancer cellsBlotting, WesternBreast NeoplasmsP-cadherinCell Line, TumorCell MembraneExtracellular SpaceGreen Fluorescent ProteinsHumansMatrix Metalloproteinase 1Matrix Metalloproteinase 2Microscopy, ConfocalNeoplasm InvasivenessRNA InterferenceCell MovementMigrationInvasionMMPssP-cadCiências Médicas::Medicina BásicaScience & TechnologyCell-cell adhesion is an elementary process in normal epithelial cellular architecture. Several studies have shown the role mediated by cadherins in this process, besides their role in the maintenance of cell polarity, differentiation and cell growth. However, during tumour progression, these molecules are frequently altered. In breast cancer, tumours that overexpress P-cadherin usually present a high histological grade, show decreased cell polarity and are associated with worse patient survival. However, little is known about how this protein dictates the very aggressive behaviour of these tumours. To achieve this goal, we set up two breast cancer cell models, where P-cadherin expression was differently modulated and analysed in terms of cell invasion, motility and migration. We show that P-cadherin overexpression, in breast cancer cells with wild-type E-cadherin, promotes cell invasion, motility and migration. Moreover, we found that the overexpression of P-cadherin induces the secretion of matrix metalloproteases, specifically MMP-1 and MMP-2, which then lead to P-cadherin ectodomain cleavage. Further, we showed that soluble P-cadherin fragment is able to induce in vitro invasion of breast cancer cells. Overall, our results contribute to elucidate the mechanism underlying the invasive behaviour of P-cadherin expressing breast tumours.scientific project (POCI/BIA-BCM/59252/2004) financed by the Portuguese Science and Technology Foundation (FCT). FCT also provided research grants as follows: Programa Ciência 2007 (FCT) for Joana Paredes, and PhD research grants for Ana Sofia Ribeiro (SFRH/BD/36096/2007) and André Albergaria (SFRH/BD/15316/2005).Springer NatureUniversidade do MinhoRibeiro, A. S.Albergaria, A.Sousa, B.Correia, A. L.Bracke, M.Seruca, R.Schmitt, F. C.Paredes, J.2010-01-212010-01-21T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/1822/67565engRibeiro, A. S., Albergaria, A., Sousa, B., Correia, A. L., et. al.(2010). Extracellular cleavage and shedding of P-cadherin: a mechanism underlying the invasive behaviour of breast cancer cells. Oncogene, 29(3), 392-4020950-92321476-559410.1038/onc.2009.33819901964https://www.nature.com/articles/onc2009338info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-07-21T12:44:40Zoai:repositorium.sdum.uminho.pt:1822/67565Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T19:42:24.442337Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Extracellular cleavage and shedding of P-cadherin: a mechanism underlying the invasive behaviour of breast cancer cells |
title |
Extracellular cleavage and shedding of P-cadherin: a mechanism underlying the invasive behaviour of breast cancer cells |
spellingShingle |
Extracellular cleavage and shedding of P-cadherin: a mechanism underlying the invasive behaviour of breast cancer cells Ribeiro, A. S. Blotting, Western Breast Neoplasms P-cadherin Cell Line, Tumor Cell Membrane Extracellular Space Green Fluorescent Proteins Humans Matrix Metalloproteinase 1 Matrix Metalloproteinase 2 Microscopy, Confocal Neoplasm Invasiveness RNA Interference Cell Movement Migration Invasion MMPs sP-cad Ciências Médicas::Medicina Básica Science & Technology |
title_short |
Extracellular cleavage and shedding of P-cadherin: a mechanism underlying the invasive behaviour of breast cancer cells |
title_full |
Extracellular cleavage and shedding of P-cadherin: a mechanism underlying the invasive behaviour of breast cancer cells |
title_fullStr |
Extracellular cleavage and shedding of P-cadherin: a mechanism underlying the invasive behaviour of breast cancer cells |
title_full_unstemmed |
Extracellular cleavage and shedding of P-cadherin: a mechanism underlying the invasive behaviour of breast cancer cells |
title_sort |
Extracellular cleavage and shedding of P-cadherin: a mechanism underlying the invasive behaviour of breast cancer cells |
author |
Ribeiro, A. S. |
author_facet |
Ribeiro, A. S. Albergaria, A. Sousa, B. Correia, A. L. Bracke, M. Seruca, R. Schmitt, F. C. Paredes, J. |
author_role |
author |
author2 |
Albergaria, A. Sousa, B. Correia, A. L. Bracke, M. Seruca, R. Schmitt, F. C. Paredes, J. |
author2_role |
author author author author author author author |
dc.contributor.none.fl_str_mv |
Universidade do Minho |
dc.contributor.author.fl_str_mv |
Ribeiro, A. S. Albergaria, A. Sousa, B. Correia, A. L. Bracke, M. Seruca, R. Schmitt, F. C. Paredes, J. |
dc.subject.por.fl_str_mv |
Blotting, Western Breast Neoplasms P-cadherin Cell Line, Tumor Cell Membrane Extracellular Space Green Fluorescent Proteins Humans Matrix Metalloproteinase 1 Matrix Metalloproteinase 2 Microscopy, Confocal Neoplasm Invasiveness RNA Interference Cell Movement Migration Invasion MMPs sP-cad Ciências Médicas::Medicina Básica Science & Technology |
topic |
Blotting, Western Breast Neoplasms P-cadherin Cell Line, Tumor Cell Membrane Extracellular Space Green Fluorescent Proteins Humans Matrix Metalloproteinase 1 Matrix Metalloproteinase 2 Microscopy, Confocal Neoplasm Invasiveness RNA Interference Cell Movement Migration Invasion MMPs sP-cad Ciências Médicas::Medicina Básica Science & Technology |
description |
Cell-cell adhesion is an elementary process in normal epithelial cellular architecture. Several studies have shown the role mediated by cadherins in this process, besides their role in the maintenance of cell polarity, differentiation and cell growth. However, during tumour progression, these molecules are frequently altered. In breast cancer, tumours that overexpress P-cadherin usually present a high histological grade, show decreased cell polarity and are associated with worse patient survival. However, little is known about how this protein dictates the very aggressive behaviour of these tumours. To achieve this goal, we set up two breast cancer cell models, where P-cadherin expression was differently modulated and analysed in terms of cell invasion, motility and migration. We show that P-cadherin overexpression, in breast cancer cells with wild-type E-cadherin, promotes cell invasion, motility and migration. Moreover, we found that the overexpression of P-cadherin induces the secretion of matrix metalloproteases, specifically MMP-1 and MMP-2, which then lead to P-cadherin ectodomain cleavage. Further, we showed that soluble P-cadherin fragment is able to induce in vitro invasion of breast cancer cells. Overall, our results contribute to elucidate the mechanism underlying the invasive behaviour of P-cadherin expressing breast tumours. |
publishDate |
2010 |
dc.date.none.fl_str_mv |
2010-01-21 2010-01-21T00:00:00Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/1822/67565 |
url |
http://hdl.handle.net/1822/67565 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Ribeiro, A. S., Albergaria, A., Sousa, B., Correia, A. L., et. al.(2010). Extracellular cleavage and shedding of P-cadherin: a mechanism underlying the invasive behaviour of breast cancer cells. Oncogene, 29(3), 392-402 0950-9232 1476-5594 10.1038/onc.2009.338 19901964 https://www.nature.com/articles/onc2009338 |
dc.rights.driver.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 |
Springer Nature |
publisher.none.fl_str_mv |
Springer Nature |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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1799132977373904896 |