Functional antagonism between STAT3 and SMAD4 regulates EMT
Data files
Mar 12, 2024 version files 4.47 MB
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KPC_ST3KOvsKPC_differential.xls
351.23 KB
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KPC_vs_KPC_KRASKO_differential.xls
460.29 KB
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MEFKP_ST3Y640FvsMEFKP_differential.xls
143.36 KB
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PDAC_KPC_KPCKRASKO_KPCSTAT3KO_fpkm.xls
3.51 MB
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README.md
2.76 KB
Abstract
Oncogenic mutations in KRAS are among the most common in cancer. Classical models suggest that loss of epithelial characteristics and the acquisition of mesenchymal traits are associated with cancer aggressiveness and therapy resistance. We identify STAT3 as a genetic modifier of TGF-beta-induced epithelial to mesenchymal transition in mutant KRAS tumors. RNA sequencing was performed with murine cells expressing mutant KRAS either overexpressing hyperactive STAT3Y640, or CRISPR-mediated knockout of STAT3, SMAD4, or KRAS. Excel files of differential expression compared to control mutant RAS cells or fpkm files are provided.
README: Functional antagonism between STAT3 and SMAD4 regulates EMT
Contributors: Stephen DAmico, Varvara Kirillov, Oleski Petrenko, and Nancy Reich
Description: We evaluated STAT3 as a cancer dependency in KRAS-mediated tumorigenesis with established models using mouse embryonic fibroblasts and pancreatic ductal adenocarcinoma cells. The data highlight antagonistic epistasis between SMAD4 and STAT3, where SMAD4 expressing tumors are poorly differentiated in the absence of STAT3, while SMAD4 deficient tumors are well-differentiated in the presence of STAT3.
Techniques: Data include RNA Sequencing analysis of genetically modified tumorigenic cells lines. Total RNA was isolated using the PureLink RNA kit (ThermoFisher) and phenol-extracted. Whole exome RNA sequencing with bioinformatics was performed by Novogene Corp..
Excel data files are included:
1) Gene ID, log fold change, and fpkm for RNA expression in KRASG12D:p53null mouse embryo fibroblasts (MEF KP)(Ischenko et al. 2013 PNAS) and MEF KP expressing hyperactive STAT3 Y640F
2) Gene ID, log fold change, and fpkm for RNA expression in Murine KRASG12D:p53R172H PDAC (KPC)(Hingorani et al. 2005 Cancer Cell) and KPC KRAS knockout cells,
3) Gene ID, log fold change, and fpkm for RNA expression in KPC and KPC STAT3 knockout cells,
4) Gene ID and fpkm for RNA expression in KPC SMAD4 knockout KPC cells
Abbreviation Description
Gene ID Ensembl gene identification number
Gene name Abbreviation of gene name
Log2 fold change log2 difference between samples
Pvalue probability difference due to chance
Padj Pvalue incorporating multiple comparison testing
Chrom chromosome number for location of gene
+ or - plus or minus gene encoding DNA strand
Start aligned numerical locus on chromosome start of cDNA sequencing
End aligned numerical locus on chromosome end of cDNA sequencing
Gene length nucleotide length of gene
Gene type protein coding, RNA, pseudogene, processed transcript
Gene description known function of protein or RNA
Readcount number of cDNA fragments sequences (reads) mapped to each gene
fpkm fragments per kilobase of million reads mapped
Methods
Total RNA was isolated using the PureLink RNA kit (ThermoFisher) and phenol-extracted. Whole exome RNA sequencing with bioinformatics was performed by Novogene Corp.. Excel data files include: 1) KRASG12D:p53null mouse embryo fibroblasts (MEF KP)(Ischenko et al. 2013 PNAS) and MEF KP expressing hyperactive STAT3 Y640F, 2) Murine KRASG12D:p53R172H PDAC (KPC)(Hingorani et al. 2005 Cancer Cell) and KPC KRAS knockout cells, 3) KPC and KPC STAT3 knockout cells, 4) KPC SMAD4 knockout cells.