p38 MAPK Down-regulates Fibulin 3 Expression through Methylation of Gene Regulatory Sequences
[EN]P38 MAPKs regulate migration and invasion. However, the mechanisms involved are only partially known. We had previously identified fibulin 3, which plays a role in migration, invasion, and tumorigenesis, as a gene regulated by p38α. We have characterized in detail how p38 MAPK regulates fibulin...
| Autores: | , , , , , , , , , , |
|---|---|
| Tipo de documento: | artigo |
| Estado: | Versão publicada |
| Data de publicação: | 2015 |
| País: | España |
| Recursos: | Universidad de Salamanca (USAL) |
| Repositório: | GREDOS. Repositorio Institucional de la Universidad de Salamanca |
| OAI Identifier: | oai:gredos.usal.es:10366/163439 |
| Acesso em linha: | http://hdl.handle.net/10366/163439 |
| Access Level: | Acceso aberto |
| Palavra-chave: | cancer biology cell signaling invasion migration Medical Oncology Cells p38 Mitogen-Activated Protein Kinases HCT116 Cells oncología médica células células HCT116 proteína cinasas p38 activadas por mitógenos |
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p38 MAPK Down-regulates Fibulin 3 Expression through Methylation of Gene Regulatory SequencesArechederra, MaríaPriego, NeiblaVázquez-Carballo, AnaSequera, CeliaGutiérrez-Uzquiza, ÁlvaroCerezo-Guisado, María IsabelOrtiz-Rivero, SaraRoncero Maíllo, CésarCuenda, AnaGuerrero Arroyo, María CarmenPorras, Almudenacancer biologycell signalinginvasionmigrationMedical OncologyCellsp38 Mitogen-Activated Protein KinasesHCT116 Cellsoncología médicacélulascélulas HCT116proteína cinasas p38 activadas por mitógenos[EN]P38 MAPKs regulate migration and invasion. However, the mechanisms involved are only partially known. We had previously identified fibulin 3, which plays a role in migration, invasion, and tumorigenesis, as a gene regulated by p38α. We have characterized in detail how p38 MAPK regulates fibulin 3 expression and its role. We describe here for the first time that p38α, p38γ, and p38δ down-regulate fibulin 3 expression. p38α has a stronger effect, and it does so through hypermethylation of CpG sites in the regulatory sequences of the gene. This would be mediated by the DNA methylase, DNMT3A, which is down-regulated in cells lacking p38α, but once re-introduced represses Fibulin 3 expression. p38α through HuR stabilizes dnmt3a mRNA leading to an increase in DNMT3A protein levels. Moreover, by knocking-down fibulin 3, we have found that Fibulin 3 inhibits migration and invasion in MEFs by mechanisms involving p38α/β inhibition. Hence, p38α pro-migratory/invasive effect might be, at least in part, mediated by fibulin 3 down-regulation in MEFs. In contrast, in HCT116 cells, Fibulin 3 promotes migration and invasion through a mechanism dependent on p38α and/or p38β activation. Furthermore, Fibulin 3 promotes in vitro and in vivo tumor growth of HCT116 cells through a mechanism dependent on p38α, which surprisingly acts as a potent inducer of tumor growth. At the same time, p38α limits fibulin 3 expression, which might represent a negative feed-back loop.Elsevier202520252015info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10366/163439reponame:GREDOS. Repositorio Institucional de la Universidad de Salamancainstname:Universidad de Salamanca (USAL)InglésAttribution-NonCommercial-NoDerivatives 4.0 Internacionalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:gredos.usal.es:10366/1634392026-06-07T06:28:51Z |
| dc.title.none.fl_str_mv |
p38 MAPK Down-regulates Fibulin 3 Expression through Methylation of Gene Regulatory Sequences |
| title |
p38 MAPK Down-regulates Fibulin 3 Expression through Methylation of Gene Regulatory Sequences |
| spellingShingle |
p38 MAPK Down-regulates Fibulin 3 Expression through Methylation of Gene Regulatory Sequences Arechederra, María cancer biology cell signaling invasion migration Medical Oncology Cells p38 Mitogen-Activated Protein Kinases HCT116 Cells oncología médica células células HCT116 proteína cinasas p38 activadas por mitógenos |
| title_short |
p38 MAPK Down-regulates Fibulin 3 Expression through Methylation of Gene Regulatory Sequences |
| title_full |
p38 MAPK Down-regulates Fibulin 3 Expression through Methylation of Gene Regulatory Sequences |
| title_fullStr |
p38 MAPK Down-regulates Fibulin 3 Expression through Methylation of Gene Regulatory Sequences |
| title_full_unstemmed |
p38 MAPK Down-regulates Fibulin 3 Expression through Methylation of Gene Regulatory Sequences |
| title_sort |
p38 MAPK Down-regulates Fibulin 3 Expression through Methylation of Gene Regulatory Sequences |
| dc.creator.none.fl_str_mv |
Arechederra, María Priego, Neibla Vázquez-Carballo, Ana Sequera, Celia Gutiérrez-Uzquiza, Álvaro Cerezo-Guisado, María Isabel Ortiz-Rivero, Sara Roncero Maíllo, César Cuenda, Ana Guerrero Arroyo, María Carmen Porras, Almudena |
| author |
Arechederra, María |
| author_facet |
Arechederra, María Priego, Neibla Vázquez-Carballo, Ana Sequera, Celia Gutiérrez-Uzquiza, Álvaro Cerezo-Guisado, María Isabel Ortiz-Rivero, Sara Roncero Maíllo, César Cuenda, Ana Guerrero Arroyo, María Carmen Porras, Almudena |
| author_role |
author |
| author2 |
Priego, Neibla Vázquez-Carballo, Ana Sequera, Celia Gutiérrez-Uzquiza, Álvaro Cerezo-Guisado, María Isabel Ortiz-Rivero, Sara Roncero Maíllo, César Cuenda, Ana Guerrero Arroyo, María Carmen Porras, Almudena |
| author2_role |
author author author author author author author author author author |
| dc.subject.none.fl_str_mv |
cancer biology cell signaling invasion migration Medical Oncology Cells p38 Mitogen-Activated Protein Kinases HCT116 Cells oncología médica células células HCT116 proteína cinasas p38 activadas por mitógenos |
| topic |
cancer biology cell signaling invasion migration Medical Oncology Cells p38 Mitogen-Activated Protein Kinases HCT116 Cells oncología médica células células HCT116 proteína cinasas p38 activadas por mitógenos |
| description |
[EN]P38 MAPKs regulate migration and invasion. However, the mechanisms involved are only partially known. We had previously identified fibulin 3, which plays a role in migration, invasion, and tumorigenesis, as a gene regulated by p38α. We have characterized in detail how p38 MAPK regulates fibulin 3 expression and its role. We describe here for the first time that p38α, p38γ, and p38δ down-regulate fibulin 3 expression. p38α has a stronger effect, and it does so through hypermethylation of CpG sites in the regulatory sequences of the gene. This would be mediated by the DNA methylase, DNMT3A, which is down-regulated in cells lacking p38α, but once re-introduced represses Fibulin 3 expression. p38α through HuR stabilizes dnmt3a mRNA leading to an increase in DNMT3A protein levels. Moreover, by knocking-down fibulin 3, we have found that Fibulin 3 inhibits migration and invasion in MEFs by mechanisms involving p38α/β inhibition. Hence, p38α pro-migratory/invasive effect might be, at least in part, mediated by fibulin 3 down-regulation in MEFs. In contrast, in HCT116 cells, Fibulin 3 promotes migration and invasion through a mechanism dependent on p38α and/or p38β activation. Furthermore, Fibulin 3 promotes in vitro and in vivo tumor growth of HCT116 cells through a mechanism dependent on p38α, which surprisingly acts as a potent inducer of tumor growth. At the same time, p38α limits fibulin 3 expression, which might represent a negative feed-back loop. |
| publishDate |
2015 |
| dc.date.none.fl_str_mv |
2015 2025 2025 |
| 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 |
http://hdl.handle.net/10366/163439 |
| url |
http://hdl.handle.net/10366/163439 |
| dc.language.none.fl_str_mv |
Inglés |
| language_invalid_str_mv |
Inglés |
| dc.rights.none.fl_str_mv |
Attribution-NonCommercial-NoDerivatives 4.0 Internacional http://creativecommons.org/licenses/by-nc-nd/4.0/ info:eu-repo/semantics/openAccess |
| rights_invalid_str_mv |
Attribution-NonCommercial-NoDerivatives 4.0 Internacional http://creativecommons.org/licenses/by-nc-nd/4.0/ |
| eu_rights_str_mv |
openAccess |
| dc.publisher.none.fl_str_mv |
Elsevier |
| publisher.none.fl_str_mv |
Elsevier |
| dc.source.none.fl_str_mv |
reponame:GREDOS. Repositorio Institucional de la Universidad de Salamanca instname:Universidad de Salamanca (USAL) |
| instname_str |
Universidad de Salamanca (USAL) |
| reponame_str |
GREDOS. Repositorio Institucional de la Universidad de Salamanca |
| collection |
GREDOS. Repositorio Institucional de la Universidad de Salamanca |
| repository.name.fl_str_mv |
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| repository.mail.fl_str_mv |
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1869403872334708736 |
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15.811543 |