| First Author | Vitos-Faleato J | Year | 2020 |
| Journal | Proc Natl Acad Sci U S A | Volume | 117 |
| Issue | 5 | Pages | 2588-2596 |
| PubMed ID | 31969449 | Mgi Jnum | J:285463 |
| Mgi Id | MGI:6389962 | Doi | 10.1073/pnas.1921404117 |
| Citation | Vitos-Faleato J, et al. (2020) Requirement for epithelial p38alpha in KRAS-driven lung tumor progression. Proc Natl Acad Sci U S A 117(5):2588-2596 |
| abstractText | 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 p38alpha as a nononcogenic signaling molecule that enables the progression of Kras(G12V)-driven lung cancer. We demonstrate in vivo that, despite acting as a tumor suppressor in healthy alveolar progenitor cells, p38alpha contributes to the proliferation and malignization of lung cancer epithelial cells. We show that high expression levels of p38alpha correlate with poor survival in lung adenocarcinoma patients, and that genetic or chemical inhibition of p38alpha halts tumor growth in lung cancer mouse models. Moreover, we reveal a lung cancer epithelial cell-autonomous function for p38alpha promoting the expression of TIMP-1, which in turn stimulates cell proliferation in an autocrine manner. Altogether, our results suggest that epithelial p38alpha promotes Kras(G12V)-driven lung cancer progression via maintenance of cellular self-growth stimulatory signals. |
