Foxm1 Mediates Cross Talk between Kras/Mitogen-Activated Protein Kinase and Canonical Wnt Pathways during Development of Respiratory Epithelium

I-Ching Wang; Jonathan Snyder; Yufang Zhang; Julie Lander; Yuto Nakafuku; James Lin; Gang Chen; Tanya V. Kalin; Jeffrey A. Whitsett; Vladimir V. Kalinichenko

doi:10.1128/MCB.00355-12

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Foxm1 Mediates Cross Talk between Kras/Mitogen-Activated Protein Kinase and Canonical Wnt Pathways during Development of Respiratory Epithelium

Journal article

Peer reviewed

Foxm1 Mediates Cross Talk between Kras/Mitogen-Activated Protein Kinase and Canonical Wnt Pathways during Development of Respiratory Epithelium

I-Ching Wang, Jonathan Snyder, Yufang Zhang, Julie Lander, Yuto Nakafuku, James Lin, Gang Chen, Tanya V. Kalin, Jeffrey A. Whitsett and Vladimir V. Kalinichenko

Molecular and cellular biology, Vol.32(19), pp.3838-3850

10/01/2012

DOI: 10.1128/MCB.00355-12

PMID: 22826436

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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 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 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.

Details

Title: Subtitle: Foxm1 Mediates Cross Talk between Kras/Mitogen-Activated Protein Kinase and Canonical Wnt Pathways during Development of Respiratory Epithelium
Creators: I-Ching Wang - Cincinnati Children's Hospital Medical Center
Jonathan Snyder - Cincinnati Children's Hospital Medical Center
Yufang Zhang - Cincinnati Children's Hospital Medical Center
Julie Lander - Cincinnati Children's Hospital Medical Center
Yuto Nakafuku - Cincinnati Children's Hospital Medical Center
James Lin - Cincinnati Children's Hospital Medical Center
Gang Chen - Cincinnati Children's Hospital Medical Center
Tanya V. Kalin - Cincinnati Children's Hospital Medical Center
Jeffrey A. Whitsett - Cincinnati Children's Hospital Medical Center
Vladimir V. Kalinichenko - Cincinnati Children's Hospital Medical Center
Resource Type: Journal article
Publication Details: Molecular and cellular biology, Vol.32(19), pp.3838-3850
DOI: 10.1128/MCB.00355-12
PMID: 22826436
ISSN: 0270-7306
eISSN: 1098-5549
Publisher: Taylor & Francis
Number of pages: 13
Language: English
Date published: 10/01/2012
Academic Unit: Orthopedics and Rehabilitation
Record Identifier: 9985237601502771

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