The p38 pathway: from biology to cancer therapy

The p38 MAPK pathway is well known for its role in transducing stress signals from the environment. Many key players and regulatory mechanisms of this signaling cascade have been described to some extent. Nevertheless, p38 participates in a broad range of cellular activities, for many of which detai...

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Autores: Martínez Limón, Adrián, Joaquin i Caudet, Manel, Caballero, María, Posas Garriga, Francesc, Nadal Clanchet, Eulàlia de
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2020
País:España
Institución:Universitat Pompeu Fabra
Repositorio:Repositorio Digital de la UPF
OAI Identifier:oai:repositori.upf.edu:10230/44274
Acceso en línea:http://hdl.handle.net/10230/44274
http://dx.doi.org/10.3390/ijms21061913
Access Level:acceso abierto
Palabra clave:SAPK
Cancer treatment
Oncogenicity
p38 MAPK
Phosphorylation
Tumor suppressor
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spelling The p38 pathway: from biology to cancer therapyMartínez Limón, AdriánJoaquin i Caudet, ManelCaballero, MaríaPosas Garriga, FrancescNadal Clanchet, Eulàlia deSAPKCancer treatmentOncogenicityp38 MAPKPhosphorylationTumor suppressorThe p38 MAPK pathway is well known for its role in transducing stress signals from the environment. Many key players and regulatory mechanisms of this signaling cascade have been described to some extent. Nevertheless, p38 participates in a broad range of cellular activities, for many of which detailed molecular pictures are still lacking. Originally described as a tumor-suppressor kinase for its inhibitory role in RAS-dependent transformation, p38 can also function as a tumor promoter, as demonstrated by extensive experimental data. This finding has prompted the development of specific inhibitors that have been used in clinical trials to treat several human malignancies, although without much success to date. However, elucidating critical aspects of p38 biology, such as isoform-specific functions or its apparent dual nature during tumorigenesis, might open up new possibilities for therapy with unexpected potential. In this review, we provide an extensive description of the main biological functions of p38 and focus on recent studies that have addressed its role in cancer. Furthermore, we provide an updated overview of therapeutic strategies targeting p38 in cancer and promising alternatives currently being explored.This work was supported by grants from the Spanish Ministry of Economy and Competitiveness (BFU2017-85152-P and FEDER to E.d.N and PGC2018-094136-B-I00 and FEDER to F.P.], the AECC Foundation [PROYE18010POSA to F.P.) and the Catalan Government (2017 SGR 799 to E.d.N and F.P.). F.P. is a recipient of an ICREA Acadèmia award (Catalan Government). We gratefully acknowledge institutional funding from the Spanish Ministry of Economy, Industry and Competitiveness (MINECO) through the Centres of Excellence Severo Ochoa award, from the CERCA Programme of the Catalan Government, and from “Unidad de Excelencia María de Maeztu,” funded by the AEI (CEX2018-000792-M).MDPI202020202020info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttp://hdl.handle.net/10230/44274http://dx.doi.org/10.3390/ijms21061913reponame:Repositorio Digital de la UPFinstname:Universitat Pompeu FabraInglésInt J Mol Sci. 2020; 21(6). pii: E1913info:eu-repo/grantAgreement/ES/2PE/BFU2017-85152-P© 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).http://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:repositori.upf.edu:10230/442742026-06-12T07:21:37Z
dc.title.none.fl_str_mv The p38 pathway: from biology to cancer therapy
title The p38 pathway: from biology to cancer therapy
spellingShingle The p38 pathway: from biology to cancer therapy
Martínez Limón, Adrián
SAPK
Cancer treatment
Oncogenicity
p38 MAPK
Phosphorylation
Tumor suppressor
title_short The p38 pathway: from biology to cancer therapy
title_full The p38 pathway: from biology to cancer therapy
title_fullStr The p38 pathway: from biology to cancer therapy
title_full_unstemmed The p38 pathway: from biology to cancer therapy
title_sort The p38 pathway: from biology to cancer therapy
dc.creator.none.fl_str_mv Martínez Limón, Adrián
Joaquin i Caudet, Manel
Caballero, María
Posas Garriga, Francesc
Nadal Clanchet, Eulàlia de
author Martínez Limón, Adrián
author_facet Martínez Limón, Adrián
Joaquin i Caudet, Manel
Caballero, María
Posas Garriga, Francesc
Nadal Clanchet, Eulàlia de
author_role author
author2 Joaquin i Caudet, Manel
Caballero, María
Posas Garriga, Francesc
Nadal Clanchet, Eulàlia de
author2_role author
author
author
author
dc.subject.none.fl_str_mv SAPK
Cancer treatment
Oncogenicity
p38 MAPK
Phosphorylation
Tumor suppressor
topic SAPK
Cancer treatment
Oncogenicity
p38 MAPK
Phosphorylation
Tumor suppressor
description The p38 MAPK pathway is well known for its role in transducing stress signals from the environment. Many key players and regulatory mechanisms of this signaling cascade have been described to some extent. Nevertheless, p38 participates in a broad range of cellular activities, for many of which detailed molecular pictures are still lacking. Originally described as a tumor-suppressor kinase for its inhibitory role in RAS-dependent transformation, p38 can also function as a tumor promoter, as demonstrated by extensive experimental data. This finding has prompted the development of specific inhibitors that have been used in clinical trials to treat several human malignancies, although without much success to date. However, elucidating critical aspects of p38 biology, such as isoform-specific functions or its apparent dual nature during tumorigenesis, might open up new possibilities for therapy with unexpected potential. In this review, we provide an extensive description of the main biological functions of p38 and focus on recent studies that have addressed its role in cancer. Furthermore, we provide an updated overview of therapeutic strategies targeting p38 in cancer and promising alternatives currently being explored.
publishDate 2020
dc.date.none.fl_str_mv 2020
2020
2020
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/10230/44274
http://dx.doi.org/10.3390/ijms21061913
url http://hdl.handle.net/10230/44274
http://dx.doi.org/10.3390/ijms21061913
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Int J Mol Sci. 2020; 21(6). pii: E1913
info:eu-repo/grantAgreement/ES/2PE/BFU2017-85152-P
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.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv reponame:Repositorio Digital de la UPF
instname:Universitat Pompeu Fabra
instname_str Universitat Pompeu Fabra
reponame_str Repositorio Digital de la UPF
collection Repositorio Digital de la UPF
repository.name.fl_str_mv
repository.mail.fl_str_mv
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