Foxm1 Mediates Cross Talk between Kras/Mitogen-Activated Protein Kinase and Canonical Wnt Pathways during Development of Respiratory Epithelium
- 1 October 2012
- journal article
- research article
- Published by Informa UK Limited in Molecular and Cellular Biology
- Vol. 32 (19), 3838-3850
- https://doi.org/10.1128/mcb.00355-12
Abstract
While Kras/mitogen-activated protein kinase (MAPK) and canonical Wnt/β-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 KrasG12D. Deletion of Foxm1 from respiratory epithelial cells during lung formation prevented structural abnormalities caused by activated KrasG12D. 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 β-catenin in vitro. Depletion of Foxm1 by short interfering RNA (siRNA) increased nuclear localization of β-catenin, increased expression of β-catenin target genes, and decreased mRNA and protein levels of the β-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/β-catenin signaling during lung development.Keywords
This publication has 63 references indexed in Scilit:
- FoxM1 Promotes β-Catenin Nuclear Localization and Controls Wnt Target-Gene Expression and Glioma TumorigenesisCancer Cell, 2011
- Increased expression of FoxM1 transcription factor in respiratory epithelium inhibits lung sacculation and causes Clara cell hyperplasiaDevelopmental Biology, 2010
- Lung OrganogenesisCurrent Topics in Developmental Biology, 2010
- Forkhead box M1 transcriptional factor is required for smooth muscle cells during embryonic development of blood vessels and esophagusDevelopmental Biology, 2009
- FoxM1, a critical regulator of oxidative stress during oncogenesisThe EMBO Journal, 2009
- Wnt2/2b and β-Catenin Signaling Are Necessary and Sufficient to Specify Lung Progenitors in the ForegutDevelopmental Cell, 2009
- Forkhead Box m1 transcription factor is required for perinatal lung functionProceedings of the National Academy of Sciences of the United States of America, 2008
- Somatic mutations affect key pathways in lung adenocarcinomaNature, 2008
- The branching programme of mouse lung developmentNature, 2008
- Jun NH 2 -terminal kinase (JNK) prevents nuclear β-catenin accumulation and regulates axis formation in Xenopus embryosProceedings of the National Academy of Sciences of the United States of America, 2006