Abstract
Molecular programs that mediate normal cell differentiation are required for oncogenesis and tumor cell survival in certain cancers. How cell-lineage-restricted genes specifically influence metastasis is poorly defined. In lung cancers, we uncovered a transcriptional program that is preferentially associated with distal airway epithelial differentiation and lung adenocarcinoma (ADC) progression. This program is regulated in part by the lineage transcription factors GATA6 and HOPX. These factors can cooperatively limit the metastatic competence of ADC cells, by modulating overlapping alveolar differentiation and invasogenic target genes. Thus, GATA6 and HOPX are critical nodes in a lineage-selective pathway that directly links effectors of airway epithelial specification to the inhibition of metastasis in the lung ADC subtype.
Copyright © 2013 Elsevier Inc. All rights reserved.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenocarcinoma / genetics
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Adenocarcinoma / pathology*
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Adenocarcinoma of Lung
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Cell Differentiation
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Cell Line, Tumor
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Cell Lineage
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Cluster Analysis
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Epithelium / pathology
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GATA6 Transcription Factor / genetics
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GATA6 Transcription Factor / metabolism
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GATA6 Transcription Factor / physiology*
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Gene Expression Regulation
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Homeodomain Proteins / genetics
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Homeodomain Proteins / metabolism
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Homeodomain Proteins / physiology*
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Humans
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Lung Neoplasms / genetics
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Lung Neoplasms / pathology*
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Neoplasm Invasiveness
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Neoplasm Metastasis / genetics
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Neoplasm Metastasis / pathology*
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Pulmonary Alveoli / cytology
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Pulmonary Alveoli / pathology
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Tumor Suppressor Proteins / genetics
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Tumor Suppressor Proteins / metabolism
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Tumor Suppressor Proteins / physiology*
Substances
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GATA6 Transcription Factor
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GATA6 protein, human
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HOPX protein, human
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Homeodomain Proteins
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Tumor Suppressor Proteins