Control of Alveolar Differentiation by the Lineage Transcription Factors GATA6 and HOPX Inhibits Lung Adenocarcinoma Metastasis (1)教程.pdf
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Cancer Cell
Article
Control of Alveolar Differentiation
by the Lineage Transcription Factors GATA6
and HOPX Inhibits Lung Adenocarcinoma Metastasis
William K.C. Cheung,1 Minghui Zhao,1 Zongzhi Liu,1 Laura E. Stevens,1 Paul D. Cao,1 Justin E. Fang,3
Thomas F. Westbrook,3 and Don X. Nguyen1,2,*
1Department of Pathology
2Yale Cancer Center
Yale University School of Medicine, New Haven, CT 06510, USA
3Department of Biochemistry, Baylor College of Medicine, Houston, TX 77030, USA
*Correspondence: don.nguyen@
/10.1016/j.ccr.2013.04.009
SUMMARY
Molecular programs that mediate normal cell differentiation are required for oncogenesis and tumor cell sur-
vival 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.
INTRODUCTION Multipotent cells from the primary lung buds differentiate into
epithelial bronchiolar or alveolar progenitors of the proximal and
Aberrant activation of cell-lineage-restricted pathways is distal airway, respectively (Morrisey and Hogan, 2010). In post-
required for oncogenic transformation in certain malignancies natal lungs, these cells may arise from regional stem cells in
(Garraway and Selle
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