Unknown,Transcriptomics,Genomics,Proteomics

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Lung adenocarcinoma metastasis is suppressed by the alveolar lineage transcription factors GATA6 and HOPX.


ABSTRACT: Molecular programs that mediate normal cell differentiation are required for oncogenesis and tumor cell survival in certain types of cancers. How cell lineage restricted genes specifically influence metastatic progression is poorly defined. In lung cancers, we uncovered an alveolar cell-selective transcriptional program that preferentially correlates with lung adenocarcinoma metastasis. This program is required for epithelial specification in the distal airways and is partially regulated by the lineage transcription factors GATA6 and HOPX. These factors cooperatively restrain the metastatic competence of adenocarcinoma cells, without affecting their survival, through the modulation of alveologenic and invasogenic target genes. Thus, GATA6 and HOPX are critical nodes in a lineage-selective pathway that directly links alveolar cell fate with metastasis suppresion in the lung adenocarcinoma subtype. mRNA profiles of human lung Adenocarcinoma PC9 cell lines infected with lentivirus harboring shRNA of control (Arab1) and shRNA of both GATA6 and HOPX were generated by deep sequencing, in triplicate, using Illumina HiSeq2000.

ORGANISM(S): Homo sapiens

SUBMITTER: zongzhi liu 

PROVIDER: E-GEOD-39121 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Control of alveolar differentiation by the lineage transcription factors GATA6 and HOPX inhibits lung adenocarcinoma metastasis.

Cheung William K C WK   Zhao Minghui M   Liu Zongzhi Z   Stevens Laura E LE   Cao Paul D PD   Fang Justin E JE   Westbrook Thomas F TF   Nguyen Don X DX  

Cancer cell 20130523 6


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  ...[more]

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