2026-04-17T16:08:51Zhttps://recercat.cat/oai/request

oai:recercat.cat:2445/1580002025-12-04T19:32:55Zcom_2072_1057col_2072_478916col_2072_478908col_2072_478917

00925njm 22002777a 4500 dc Vitos Faleato, Jessica author Real, Sebastian author Gutierrez Prat, Núria author Villanueva Garatachea, Alberto author Llonch, Elisabet author Drosten, Matthias author Barbacid, Mariano author Nebreda, Àngel R. author 2020-04-29T08:07:57Z 2020-07-22T05:10:29Z 2020-01-22 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. Cèl·lules epitelials Càncer de pulmó Epithelial cells Lung cancer Requirement for epithelial p38α in KRAS-driven lung tumor progression