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Title: Requirement for epithelial p38α in KRAS-driven lung tumor progression
Author: Vitos Faleato, Jessica
Real, Sebastian
Gutierrez Prat, Núria
Villanueva Garatachea, Alberto
Llonch, Elisabet
Drosten, Matthias
Barbacid, Mariano
Nebreda, Àngel R.
Keywords: Cèl·lules epitelials
Càncer de pulmó
Epithelial cells
Lung cancer
Issue Date: 22-Jan-2020
Publisher: National Academy of Sciences
Abstract: 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.
Note: Versió postprint del document publicat a:
It is part of: PNAS, 2020, vol. 117, num. 5, p. 2588-2596
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Appears in Collections:Articles publicats en revistes (Institut de Recerca Biomèdica (IRB Barcelona))
Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

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