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