| First Author | Wang IC | Year | 2012 |
| Journal | Mol Cell Biol | Volume | 32 |
| Issue | 19 | Pages | 3838-50 |
| PubMed ID | 22826436 | Mgi Jnum | J:188926 |
| Mgi Id | MGI:5442634 | Doi | 10.1128/MCB.00355-12 |
| Citation | Wang IC, et al. (2012) Foxm1 mediates cross talk between Kras/mitogen-activated protein kinase and canonical Wnt pathways during development of respiratory epithelium. Mol Cell Biol 32(19):3838-50 |
| abstractText | While Kras/mitogen-activated protein kinase (MAPK) and canonical Wnt/beta-catenin are critical for lung morphogenesis, mechanisms integrating these important signaling pathways during lung development are unknown. Herein, we demonstrate that the Foxm1 transcription factor is a key downstream target of activated Kras(G12D). Deletion of Foxm1 from respiratory epithelial cells during lung formation prevented structural abnormalities caused by activated Kras(G12D). Kras/Foxm1 signaling inhibited the activity of canonical Wnt signaling in the developing lung in vivo. Foxm1 decreased T-cell factor (TCF) transcriptional activity induced by activated beta-catenin in vitro. Depletion of Foxm1 by short interfering RNA (siRNA) increased nuclear localization of beta-catenin, increased expression of beta-catenin target genes, and decreased mRNA and protein levels of the beta-catenin inhibitor Axin2. Axin2 mRNA was reduced in distal lung epithelium of Foxm1-deficient mice. Foxm1 directly bound to and increased transcriptional activity of the Axin2 promoter region. Foxm1 is required for Kras signaling in distal lung epithelium and provides a mechanism integrating Kras and canonical Wnt/beta-catenin signaling during lung development. |
