Requirement for epithelial p38α in KRAS-driven lung tumor progression.

Malignant transformation entails important changes in the control of cell proliferation through the rewiring of selected signaling pathways. Cancer cells then become very dependent on the proper function of those pathways, and their inhibition offers therapeutic opportunities. Here we identify the s...

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Autores: Vitos-Faleato, Jessica, Real, Sebastián M, Gutierrez-Prat, Nuria, Villanueva, Alberto, Llonch, Elisabet, Drosten, Matthias, Barbacid, Mariano, Nebreda, Angel R
Tipo de recurso: artículo
Fecha de publicación:2020
País:España
Institución:Instituto de Salud Carlos III (ISCIII)
Repositorio:Repisalud
Idioma:inglés
OAI Identifier:oai:repisalud.isciii.es:20.500.12105/18187
Acceso en línea:http://hdl.handle.net/20.500.12105/18187
Access Level:acceso abierto
Palabra clave:Adenocarcinoma of Lung
Animals
Cell Line, Tumor
Cell Proliferation
Disease Models, Animal
Disease Progression
Humans
Lung
Lung Neoplasms
Mice
Mice, Inbred C57BL
Mitogen-Activated Protein Kinase 14
Neoplastic Processes
Proto-Oncogene Proteins p21(ras)
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oai_identifier_str oai:repisalud.isciii.es:20.500.12105/18187
network_acronym_str ES
network_name_str España
repository_id_str
spelling Requirement for epithelial p38α in KRAS-driven lung tumor progression.Vitos-Faleato, JessicaReal, Sebastián MGutierrez-Prat, NuriaVillanueva, AlbertoLlonch, ElisabetDrosten, MatthiasBarbacid, MarianoNebreda, Angel RAdenocarcinoma of LungAnimalsCell Line, TumorCell ProliferationDisease Models, AnimalDisease ProgressionHumansLungLung NeoplasmsMiceMice, Inbred C57BLMitogen-Activated Protein Kinase 14Neoplastic ProcessesProto-Oncogene Proteins p21(ras)Malignant transformation entails important changes in the control of cell proliferation through the rewiring of selected signaling pathways. Cancer cells then become very dependent on the proper function of those pathways, and their inhibition offers therapeutic opportunities. Here we identify the stress kinase p38α as a nononcogenic signaling molecule that enables the progression of KrasG12V-driven lung cancer. We demonstrate in vivo that, despite acting as a tumor suppressor in healthy alveolar progenitor cells, p38α contributes to the proliferation and malignization of lung cancer epithelial cells. We show that high expression levels of p38α correlate with poor survival in lung adenocarcinoma patients, and that genetic or chemical inhibition of p38α halts tumor growth in lung cancer mouse models. Moreover, we reveal a lung cancer epithelial cell-autonomous function for p38α promoting the expression of TIMP-1, which in turn stimulates cell proliferation in an autocrine manner. Altogether, our results suggest that epithelial p38α promotes KrasG12V-driven lung cancer progression via maintenance of cellular self-growth stimulatory signals.National Academy of SciencesUnión Europea. Comisión Europea. European Research Council (ERC)Ministerio de Ciencia, Innovación y Universidades (España)Fundación BBVACentres de Recerca de Catalunya (CERCA)20242024-02-1320202020-02-0420202020-02-04journal articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/20.500.12105/18187reponame:Repisaludinstname:Instituto de Salud Carlos III (ISCIII)InglésengEuropean Commission http://dx.doi.org/10.13039/501100000780 Seventh Framework Programme 294665open accesshttp://purl.org/coar/access_right/c_abf2Attribution-NonCommercial-NoDerivatives 4.0 Internacionalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:repisalud.isciii.es:20.500.12105/181872026-06-12T12:43:37Z
dc.title.none.fl_str_mv Requirement for epithelial p38α in KRAS-driven lung tumor progression.
title Requirement for epithelial p38α in KRAS-driven lung tumor progression.
spellingShingle Requirement for epithelial p38α in KRAS-driven lung tumor progression.
Vitos-Faleato, Jessica
Adenocarcinoma of Lung
Animals
Cell Line, Tumor
Cell Proliferation
Disease Models, Animal
Disease Progression
Humans
Lung
Lung Neoplasms
Mice
Mice, Inbred C57BL
Mitogen-Activated Protein Kinase 14
Neoplastic Processes
Proto-Oncogene Proteins p21(ras)
title_short Requirement for epithelial p38α in KRAS-driven lung tumor progression.
title_full Requirement for epithelial p38α in KRAS-driven lung tumor progression.
title_fullStr Requirement for epithelial p38α in KRAS-driven lung tumor progression.
title_full_unstemmed Requirement for epithelial p38α in KRAS-driven lung tumor progression.
title_sort Requirement for epithelial p38α in KRAS-driven lung tumor progression.
dc.creator.none.fl_str_mv Vitos-Faleato, Jessica
Real, Sebastián M
Gutierrez-Prat, Nuria
Villanueva, Alberto
Llonch, Elisabet
Drosten, Matthias
Barbacid, Mariano
Nebreda, Angel R
author Vitos-Faleato, Jessica
author_facet Vitos-Faleato, Jessica
Real, Sebastián M
Gutierrez-Prat, Nuria
Villanueva, Alberto
Llonch, Elisabet
Drosten, Matthias
Barbacid, Mariano
Nebreda, Angel R
author_role author
author2 Real, Sebastián M
Gutierrez-Prat, Nuria
Villanueva, Alberto
Llonch, Elisabet
Drosten, Matthias
Barbacid, Mariano
Nebreda, Angel R
author2_role author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Unión Europea. Comisión Europea. European Research Council (ERC)
Ministerio de Ciencia, Innovación y Universidades (España)
Fundación BBVA
Centres de Recerca de Catalunya (CERCA)
dc.subject.none.fl_str_mv Adenocarcinoma of Lung
Animals
Cell Line, Tumor
Cell Proliferation
Disease Models, Animal
Disease Progression
Humans
Lung
Lung Neoplasms
Mice
Mice, Inbred C57BL
Mitogen-Activated Protein Kinase 14
Neoplastic Processes
Proto-Oncogene Proteins p21(ras)
topic Adenocarcinoma of Lung
Animals
Cell Line, Tumor
Cell Proliferation
Disease Models, Animal
Disease Progression
Humans
Lung
Lung Neoplasms
Mice
Mice, Inbred C57BL
Mitogen-Activated Protein Kinase 14
Neoplastic Processes
Proto-Oncogene Proteins p21(ras)
description Malignant transformation entails important changes in the control of cell proliferation through the rewiring of selected signaling pathways. Cancer cells then become very dependent on the proper function of those pathways, and their inhibition offers therapeutic opportunities. Here we identify the stress kinase p38α as a nononcogenic signaling molecule that enables the progression of KrasG12V-driven lung cancer. We demonstrate in vivo that, despite acting as a tumor suppressor in healthy alveolar progenitor cells, p38α contributes to the proliferation and malignization of lung cancer epithelial cells. We show that high expression levels of p38α correlate with poor survival in lung adenocarcinoma patients, and that genetic or chemical inhibition of p38α halts tumor growth in lung cancer mouse models. Moreover, we reveal a lung cancer epithelial cell-autonomous function for p38α promoting the expression of TIMP-1, which in turn stimulates cell proliferation in an autocrine manner. Altogether, our results suggest that epithelial p38α promotes KrasG12V-driven lung cancer progression via maintenance of cellular self-growth stimulatory signals.
publishDate 2020
dc.date.none.fl_str_mv 2020
2020-02-04
2020
2020-02-04
2024
2024-02-13
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/20.500.12105/18187
url http://hdl.handle.net/20.500.12105/18187
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.relation.none.fl_str_mv European Commission http://dx.doi.org/10.13039/501100000780 Seventh Framework Programme 294665
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution-NonCommercial-NoDerivatives 4.0 Internacional
http://creativecommons.org/licenses/by-nc-nd/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution-NonCommercial-NoDerivatives 4.0 Internacional
http://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv National Academy of Sciences
publisher.none.fl_str_mv National Academy of Sciences
dc.source.none.fl_str_mv reponame:Repisalud
instname:Instituto de Salud Carlos III (ISCIII)
instname_str Instituto de Salud Carlos III (ISCIII)
reponame_str Repisalud
collection Repisalud
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869407544036818945
score 15,81155

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