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Title: Nkx2.1 represses a latent gastric differentiation program in lung adenocarcinoma      
keywords:
Transcriptome or Gene expression
ID:
PRJNA153501
description:
During cancer evolution, cellular differentiation programs become dysregulated. The transcription factor Nkx2-1 is a master regulator of pulmonary differentiation that is downregulated in poorly differentiated lung adenocarcinoma. Here we use conditional murine genetics to study the fate of lung epithelial cells upon loss of their master cell fate regulator. Nkx2-1 deletion in normal and neoplastic lung causes not only loss of pulmonary identity but also gastric transdifferentiation. Nkx2-1 maintains pulmonary identity by sequestering the Foxa1 transcription factor at lung-specific loci and inhibiting Foxa1 binding to gastrointestinal targets. Murine Nkx2-1-negative lung tumors mimic the mucinous subtype of human lung adenocarcinoma, which also exhibits gastric transdifferentiation. Nkx2-1-negative lung adenocarcinomas are dependent on the gastrointestinal gene Hnf4a for efficient initiation. Thus, loss of Nkx2-1 results in transdifferentiation rather than stable dedifferentiation in vivo, suggesting that inactivation of both active and latent differentiation programs may be required for tumors to reach a primitive, dedifferentiated state. Overall design: The study was designed to compare the expression profiles of Nkx2-1-positive lung adenocarcinomas with tumors in which Nkx2-1 was deleted at the time of initiation or 6-7 months after initiation.
accesstypes:
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landingpage: http://www.ncbi.nlm.nih.gov/bioproject/PRJNA153501
authentication:
none
authorization:
none
ID:
pmid:23523371
name:
Mus musculus
ncbiID:
ncbitax:10090
abbreviation:
NCBI
homePage: http://www.ncbi.nlm.nih.gov
ID:
SCR:006472
name:
National Center for Biotechnology Information
homePage: http://www.ncbi.nlm.nih.gov/bioproject
ID:
SCR:004801
name:
NCBI BioProject
  • P30 CA014051/CA/NCI NIH HHS/United States

  • U01 CA084306/CA/NCI NIH HHS/United States

  • K08-CA154784-01/CA/NCI NIH HHS/United States

  • R01 CA109038/CA/NCI NIH HHS/United States

  • Howard Hughes Medical Institute/United States

  • K08 CA154784/CA/NCI NIH HHS/United States

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