2026-05-21T23:06:45Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/181872024-11-30T00:13:55Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597
Repisalud
author
Vitos-Faleato, Jessica
author
Real, Sebastián M
author
Gutierrez-Prat, Nuria
author
Villanueva, Alberto
author
Llonch, Elisabet
author
Drosten, Matthias
author
Barbacid, Mariano
author
Nebreda, Angel R
funder
Unión Europea. Comisión Europea. European Research Council (ERC)
funder
Ministerio de Ciencia, Innovación y Universidades (España)
funder
Fundación BBVA
funder
Centres de Recerca de Catalunya (CERCA)
2024-02-13T10:50:23Z
2024-02-13T10:50:23Z
2020-02-04
Proc Natl Acad Sci U S A . 2020 ;117(5):2588-2596.
10.1073/pnas.1921404117
1091-6490
Proceedings of the National Academy of Sciences of the United States of America
31969449
http://hdl.handle.net/20.500.12105/18187
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.
eng
Requirement for epithelial p38α in KRAS-driven lung tumor progression.
journal article
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Requirementforepithelialp38αin_2020.pdf
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https://repisalud.isciii.es/bitstreams/0b330d9f-8b10-4584-bb0a-d29294297f77/download
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Requirementforepithelialp38αin_2020.pdf.txt