Sos1 ablation alters focal adhesion dynamics and increases Mmp2/9-dependent gelatinase activity in primary mouse embryonic fibroblasts

Background Sos1 and Sos2 are guanine-nucleotide exchange factors for Ras and Rac small GTPases, which are involved in a wide range of cellular responses including proliferation and migration. We have previously shown that Sos1 and Sos2 have different effects on cell migration, but the underlying mec...

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Autores: Liceras-Boillos, Pilar, Garcia-Navas, Rósula, Llorente-González, Clara, Lorenzo-Martin, L. Francisco, Luna-Ramírez, Luis, Fuentes-Mateos, Rocío, Calvo Baltanás, Fernando
Tipo de documento: artigo
Estado:Versão publicada
Data de publicação:2025
País:España
Recursos:Universidad de Sevilla (US)
Repositório:idUS. Depósito de Investigación de la Universidad de Sevilla
OAI Identifier:oai:idus.us.es:11441/169728
Acesso em linha:https://hdl.handle.net/11441/169728
https://doi.org/10.1186/s12964-025-02122-1
Access Level:Acceso aberto
Palavra-chave:Sos1
Sos2
RasGEF
Ras
Rac
Migration
Mmp2/9
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spelling Sos1 ablation alters focal adhesion dynamics and increases Mmp2/9-dependent gelatinase activity in primary mouse embryonic fibroblastsLiceras-Boillos, PilarGarcia-Navas, RósulaLlorente-González, ClaraLorenzo-Martin, L. FranciscoLuna-Ramírez, LuisFuentes-Mateos, RocíoCalvo Baltanás, FernandoSos1Sos2RasGEFRasRacMigrationMmp2/9Background Sos1 and Sos2 are guanine-nucleotide exchange factors for Ras and Rac small GTPases, which are involved in a wide range of cellular responses including proliferation and migration. We have previously shown that Sos1 and Sos2 have different effects on cell migration, but the underlying mechanisms are not clear. Methods Using a 4-hydroxytamoxifen-inducible conditional Sos1KO mutation, here we evaluated the functional specificity or redundancy of Sos1 and Sos2 regarding the control of cell migration and dynamics of focal adhesions (FAs) in primary mouse embryonic fibroblasts (MEFs). Results Functional analysis of the transcriptome of primary Sos1/2WT, Sos1KO, Sos2KO and Sos1/2DKO-MEFs revealed a specific, dominant role of Sos1 over Sos2 in transcriptional regulation. Sos1KO MEFs had an increased number and stability of focal adhesions (FAs) and curbed protrusion and spreading. Conversely, Sos2KO MEFs displayed unstable FAs with increased protrusion. Interestingly, Sos1, but not Sos2, ablation reduced the levels of GTP-bound Rac at the leading edge. In 3D, however, only Sos1/2KO MEFs showed increased invasion and matrix degradative capacity, which correlated with increased expression of the Mmp2 and Mmp9 gelatinases. Moreover, increased matrix degradation in Sos1/2KO MEFs was abrogated by treatment with Mmp2/9 inhibitors. Conclusions Our data demonstrate that Sos1 and Sos2 have different functions in FAs distribution and dynamics in 2D whereas in 3D they act together to regulate invasion and unveil a previously undescribed mechanistic connection between Sos1/2 and the regulation of Mmp2/9 expression in primary MEFs.Biomed central LTDFisiología Médica y BiofísicaCTS007: Fisiopatología de células madre neurales2025info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttps://hdl.handle.net/11441/169728https://doi.org/10.1186/s12964-025-02122-1reponame:idUS. Depósito de Investigación de la Universidad de Sevillainstname:Universidad de Sevilla (US)InglésCell communication and signaling, 23 (1).https://biosignaling.biomedcentral.com/articles/10.1186/s12964-025-02122-1info:eu-repo/semantics/openAccessoai:idus.us.es:11441/1697282026-06-17T12:51:07Z
dc.title.none.fl_str_mv Sos1 ablation alters focal adhesion dynamics and increases Mmp2/9-dependent gelatinase activity in primary mouse embryonic fibroblasts
title Sos1 ablation alters focal adhesion dynamics and increases Mmp2/9-dependent gelatinase activity in primary mouse embryonic fibroblasts
spellingShingle Sos1 ablation alters focal adhesion dynamics and increases Mmp2/9-dependent gelatinase activity in primary mouse embryonic fibroblasts
Liceras-Boillos, Pilar
Sos1
Sos2
RasGEF
Ras
Rac
Migration
Mmp2/9
title_short Sos1 ablation alters focal adhesion dynamics and increases Mmp2/9-dependent gelatinase activity in primary mouse embryonic fibroblasts
title_full Sos1 ablation alters focal adhesion dynamics and increases Mmp2/9-dependent gelatinase activity in primary mouse embryonic fibroblasts
title_fullStr Sos1 ablation alters focal adhesion dynamics and increases Mmp2/9-dependent gelatinase activity in primary mouse embryonic fibroblasts
title_full_unstemmed Sos1 ablation alters focal adhesion dynamics and increases Mmp2/9-dependent gelatinase activity in primary mouse embryonic fibroblasts
title_sort Sos1 ablation alters focal adhesion dynamics and increases Mmp2/9-dependent gelatinase activity in primary mouse embryonic fibroblasts
dc.creator.none.fl_str_mv Liceras-Boillos, Pilar
Garcia-Navas, Rósula
Llorente-González, Clara
Lorenzo-Martin, L. Francisco
Luna-Ramírez, Luis
Fuentes-Mateos, Rocío
Calvo Baltanás, Fernando
author Liceras-Boillos, Pilar
author_facet Liceras-Boillos, Pilar
Garcia-Navas, Rósula
Llorente-González, Clara
Lorenzo-Martin, L. Francisco
Luna-Ramírez, Luis
Fuentes-Mateos, Rocío
Calvo Baltanás, Fernando
author_role author
author2 Garcia-Navas, Rósula
Llorente-González, Clara
Lorenzo-Martin, L. Francisco
Luna-Ramírez, Luis
Fuentes-Mateos, Rocío
Calvo Baltanás, Fernando
author2_role author
author
author
author
author
author
dc.contributor.none.fl_str_mv Fisiología Médica y Biofísica
CTS007: Fisiopatología de células madre neurales
dc.subject.none.fl_str_mv Sos1
Sos2
RasGEF
Ras
Rac
Migration
Mmp2/9
topic Sos1
Sos2
RasGEF
Ras
Rac
Migration
Mmp2/9
description Background Sos1 and Sos2 are guanine-nucleotide exchange factors for Ras and Rac small GTPases, which are involved in a wide range of cellular responses including proliferation and migration. We have previously shown that Sos1 and Sos2 have different effects on cell migration, but the underlying mechanisms are not clear. Methods Using a 4-hydroxytamoxifen-inducible conditional Sos1KO mutation, here we evaluated the functional specificity or redundancy of Sos1 and Sos2 regarding the control of cell migration and dynamics of focal adhesions (FAs) in primary mouse embryonic fibroblasts (MEFs). Results Functional analysis of the transcriptome of primary Sos1/2WT, Sos1KO, Sos2KO and Sos1/2DKO-MEFs revealed a specific, dominant role of Sos1 over Sos2 in transcriptional regulation. Sos1KO MEFs had an increased number and stability of focal adhesions (FAs) and curbed protrusion and spreading. Conversely, Sos2KO MEFs displayed unstable FAs with increased protrusion. Interestingly, Sos1, but not Sos2, ablation reduced the levels of GTP-bound Rac at the leading edge. In 3D, however, only Sos1/2KO MEFs showed increased invasion and matrix degradative capacity, which correlated with increased expression of the Mmp2 and Mmp9 gelatinases. Moreover, increased matrix degradation in Sos1/2KO MEFs was abrogated by treatment with Mmp2/9 inhibitors. Conclusions Our data demonstrate that Sos1 and Sos2 have different functions in FAs distribution and dynamics in 2D whereas in 3D they act together to regulate invasion and unveil a previously undescribed mechanistic connection between Sos1/2 and the regulation of Mmp2/9 expression in primary MEFs.
publishDate 2025
dc.date.none.fl_str_mv 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 https://hdl.handle.net/11441/169728
https://doi.org/10.1186/s12964-025-02122-1
url https://hdl.handle.net/11441/169728
https://doi.org/10.1186/s12964-025-02122-1
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Cell communication and signaling, 23 (1).
https://biosignaling.biomedcentral.com/articles/10.1186/s12964-025-02122-1
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Biomed central LTD
publisher.none.fl_str_mv Biomed central LTD
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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score 15,811543

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