Comment[ArrayExpressAccession] E-GEOD-39121 MAGE-TAB Version 1.1 Public Release Date 2013-06-10 Investigation Title Lung adenocarcinoma metastasis is suppressed by the alveolar lineage transcription factors GATA6 and HOPX. Comment[Submitted Name] Lung adenocarcinoma metastasis is suppressed by the alveolar lineage transcription factors GATA6 and HOPX. Experiment Description 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. Term Source Name ArrayExpress EFO Term Source File http://www.ebi.ac.uk/arrayexpress/ http://www.ebi.ac.uk/efo/efo.owl Person Last Name liu Zongzhi Don Person First Name zongzhi Liu Nguyen Person Email zongzhi.liu@yale.edu Person Affiliation Yale University Person Phone 203-737-3455 Person Address Pathology, Yale University, 310 Cedar St, New Haven, CT, USA Person Roles submitter Protocol Name P-GSE39121-4 P-GSE39121-1 P-GSE39121-3 P-GSE39121-2 Protocol Description Illumina Casava software used for basecalling. Sequenced reads were mapped to human transcriptome using tophat 1.4.1 with parameters -p4 --solexa-quals --min-anchor 12 --library-type fr-unstranded -G All_Isoforms_For_ExpressionTable.gtf Reads per gene was calculated using HtSeq-count in union mode Reads per gene was nomalized to the library size and differential expressed genes was detected using EdgeR R package. Genome_build: hg19 Supplementary_files_format_and_content: tab-delimited text files include normalized count of reads for each gene and each sample. Doxycycline (1ug/ml) for 5 days Illumina TrueSeq RNA Prep, Total RNA from triplicate samples were extracted using RNeasy Mini kit (Qiagen). The quality of RNA samples was first analyzed on Agilent Bioanalyzer. Single-end, barcoded sequence libraries were constructed with TruSeq RNA Sample Prep Kit (Illumina) and sequenced on a HiSeq 2000 instrument according to the manufacturer’s instructions with single-end 50 base pair reads. RPMI1640 + 10%FBS Protocol Type normalization data transformation protocol sample treatment protocol nucleic acid library construction protocol growth protocol Experimental Factor Name infect Experimental Factor Type infect Comment[SecondaryAccession] GSE39121 Comment[GEOReleaseDate] 2013-06-10 Comment[ArrayExpressSubmissionDate] 2012-07-05 Comment[GEOLastUpdateDate] 2013-06-21 Comment[AEExperimentType] RNA-seq of coding RNA Comment[AdditionalFile:Data1] GSE39121_counts_normalized_shCtrl_shGata6Hopx.txt Comment[SecondaryAccession] SRP014027 Comment[SequenceDataURI] http://www.ebi.ac.uk/ena/data/view/SRR518622-SRR518627 SDRF File E-GEOD-39121.sdrf.txt Publication Title Control of alveolar differentiation by the lineage transcription factors GATA6 and HOPX inhibits lung adenocarcinoma metastasis. Publication Author List Cheung WK, Zhao M, Liu Z, Stevens LE, Cao PD, Fang JE, Westbrook TF, Nguyen DX PubMed ID 23707782 Publication DOI 10.1016/j.ccr.2013.04.009