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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Sep 01, 2021 |
| Title |
STAT3 promotes melanoma metastasis by CEBP-induced repression of the MITF pigmentation pathway |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Metastatic melanoma is hallmarked by its ability to switch oncogenic MITF expression. Here we tested the impact of STAT3 on melanoma onset and progression in association with MITF expression levels. We established a mouse melanoma model for deleting Stat3 specifically in melanocytes with specific expression of human hyperactive NRASQ61K in an Ink4a deficient background. Mice with tissue specific Stat3 deletion showed an early onset of disease, but displayed significantly diminished lung metastasis. Whole genome expression profiling also revealed a reduced invasion phenotype, which was functionally confirmed in 3D melanoma model systems. Notably, loss or knockdown of STAT3 in mouse or human cells resulted in up-regulation of MITF and induction of cell proliferation. Mechanistically we show that STAT3 induced CEBPa/b expression was sufficient to suppress MITF transcription. Epigenetic analysis by ATAC-seq confirmed that STAT3 enabled CEBPa/b binding to the MITF enhancer region thereby silencing it. We conclude that STAT3 is a metastasis driver able to antagonize the MITF oncogene via direct induction of CEBP family member transcription facilitating RAS-RAF-driven melanoma metastasis.
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| Overall design |
ATAC sequencing of mouse melanoma cell lines with Stat3 knockout and respective wild type controls.
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| Contributor(s) |
Swoboda A, Soukup R, Kinslechner K, Wingelhofer B, Schörghofer D, Sternberg C, Pham HT, Vallianou M, Horvath J, Stoiber D, Kenner L, Larue L, Poli V, Beermann F, Yokota T, Kubicek S, Krausgruber T, Rendeiro AF, Bock C, Zenz R, Kovacic B, Aberger F, Hengstschläger M, Petzelbauer P, Mikula M, Moriggl R |
| Citation(s) |
33323974 |
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| Submission date |
Sep 05, 2018 |
| Last update date |
Sep 02, 2021 |
| Contact name |
Christoph Bock |
| E-mail(s) |
cbock@cemm.oeaw.ac.at
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| Organization name |
CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences
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| Street address |
Lazarettgasse 14
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| City |
Vienna |
| ZIP/Postal code |
1090 |
| Country |
Austria |
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| Platforms (1) |
| GPL21103 |
Illumina HiSeq 4000 (Mus musculus) |
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| Samples (8)
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| Relations |
| BioProject |
PRJNA489483 |
| SRA |
SRP159679 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE119540_RAW.tar |
1.5 Gb |
(http)(custom) |
TAR (of BIGWIG, NARROWPEAK) |
| GSE119540_melanoma_stat3_peaks.raw_coverage.csv.gz |
3.2 Mb |
(ftp)(http) |
CSV |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
| Processed data are available on Series record |
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