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Series GSE65261 Query DataSets for GSE65261
Status Public on Nov 04, 2015
Title Ets-domain transcription factor Ets21c and nuclear receptor Ftz-F1 are novel effectors of JNK promoting tumor malignancy
Organism Drosophila melanogaster
Experiment type Expression profiling by high throughput sequencing
Summary Cancer represents a complex family of diseases, characterized by the uncontrolled malignant growth of a particular cell type and by metastatic dissemination of these transformed cells to secondary sites. The hallmark tumor features emerge as a result of aberrant cellular signaling and pathological gene expression driven by cooperating genetic lesions. Being the convergence points of signaling pathways, transcription factors play crucial roles in cancer. Here, we define a transcription factor network that triggers an abnormal gene expression program promoting malignancy of clonal tumors, generated in Drosophila imaginal disc epithelium by overexpressing oncogenic Ras (RasV12) in a background lacking the tumor suppressor gene scribble (scrib1). We show that the nuclear receptor Ftz-F1 and the ETS-domain transcription factor Ets21c are upregulated in the rasV12scrib1 tumors in response to activated Jun-N-terminal kinase (JNK) signaling. Depletion of either Ftz-F1 or Ets21c improves viability of Drosophila larvae suffering from tumors, and this effect can be further enhanced by simultaneous removal of the Jun-dimerizing partner Fos. We identified Fos as a key mediator of JNK-induced differentiation defects and further show that Ftz-F1 and Fos are required for tumor invasiveness. However, only Ets21c can efficiently substitute for JNK and cooperate with RasV12 to induce invasive tumors that recapitulate hallmarks of malignant rasV12scrib1 tumors including elevated matrix metalloprotease (MMP1) and insulin-like peptide 8 (Dilp8) expression. In conclusion, our study provides functional evidence for a network of cooperating transcription factor that dictates target gene expression and promotes tumor phenotypes in response to aberrant JNK signaling.
Overall design 20 samples analyzed, 4 control samples
Contributor(s) K├╝lshammer E, Mundorf J, Kilinc M, Frommolt P, Wagle P, Uhlirova M
Citation(s) 26398940
Submission date Jan 23, 2015
Last update date May 15, 2019
Contact name Mirka Uhlirova
Organization name CECAD Research Center Cologne
Department Institute for Genetics
Lab Uhlirova Lab
Street address Joseph-Stelzmann Str. 26
City Cologne
State/province NRW
ZIP/Postal code 50931
Country Germany
Platforms (1)
GPL13304 Illumina HiSeq 2000 (Drosophila melanogaster)
Samples (20)
GSM1591021 FRT82B_1
GSM1591022 FRT82B_2
GSM1591023 FRT82B_3
BioProject PRJNA273558
SRA SRP052809

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SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE65261_RAW.tar 6.1 Mb (http)(custom) TAR (of XLS)
GSE65261_Regulated_Genes_5kbUpstream.bed.gz 58.0 Kb (ftp)(http) BED
GSE65261_Regulated_Genes_Intron1.bed.gz 49.0 Kb (ftp)(http) BED
GSE65261_Table_S1_transcriptome_analysis.xlsx 1.6 Mb (ftp)(http) XLSX
GSE65261_readme.txt 467 b (ftp)(http) TXT
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file
Processed data are available on Series record

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