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GEO help: Mouse over screen elements for information. |
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| Status |
Public on May 06, 2019 |
| Title |
An ErbB2/c-Src axis drives mammary tumorigenesis through metabolically directed translational regulation of Polycomb Repressor Complex 2 [ChIP-Seq] |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Perturbations in histone modifications alter transcription and promote carcinogenesis. Breast cancers frequently overexpress the histone methyltransferase EZH2, the catalytic subunit of Polycomb Repressor Complex 2 (PRC2). However, the mechanisms driving EZH2 overexpression are obscure and elucidating the role of PRC2 in breast cancer, which is highly heterogeneous, is challenging given its context-dependent oncogenic and tumor suppressive functions. Here, using genetically engineered mouse, PDX and cell line models, we show that the tyrosine kinase c-Src links energy sufficiency with PRC2 subunit overexpression via control of mRNA translation. In breast cancers initiated by the oncogene ErbB2, c-Src stimulates mitochondrial ATP production to suppress energy stress and permit sustained activation of the mammalian/mechanistic target of rapamycin complex 1 (mTORC1), which increases the translation of mRNAs encoding the PRC2 subunits Ezh2 and Suz12. We show that Ezh2 overexpression and activity are pivotal in ErbB2-mediated mammary tumorigenesis. These results reveal the hitherto unknown c-Src/mTORC1/PRC2 axis, which is essential for ErbB2-driven carcinogenesis.
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| Overall design |
ChIP Seq of H3K27me3 in c-Src-deficient ErbB2+ murine mammary tumor cell lines and control, wild-type ErbB2+ mammary tumor cell lines. 2 biological replicates per genotype were sequenced.
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| Contributor(s) |
Muller WJ, Smith HW |
| Citation(s) |
31263101 |
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| Submission date |
May 06, 2019 |
| Last update date |
Jul 09, 2019 |
| Contact name |
Harvey Wilmore Smith |
| E-mail(s) |
harvey.smith2@mcgill.ca
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| Organization name |
McGill University
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| Department |
Goodman Cancer Research Centre
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| Street address |
Life Sciences Complex, Room 602, 1160 Pine Avenue West
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| City |
Montreal |
| State/province |
Quebec |
| ZIP/Postal code |
H3A 1A3 |
| Country |
Canada |
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| Platforms (1) |
| GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
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| Samples (8)
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| GSM3752705 |
Breast cancer cell line, WT, 8905 WT H3K27me3 ChIP-Seq |
| GSM3752706 |
Breast cancer cell line, WT, 9822 WT H3K27me3 ChIP-Seq |
| GSM3752707 |
Breast cancer cell line, WT, 8905 WT input DNA |
| GSM3752708 |
Breast cancer cell line, WT, 9822 WT input DNA |
| GSM3752709 |
Breast cancer cell line, cSrcKO, 4447 KO H3K27me3 ChIP-Seq |
| GSM3752710 |
Breast cancer cell line, cSrcKO, 9327 KO H3K27me3 ChIP-Seq |
| GSM3752711 |
Breast cancer cell line, cSrcKO, 4447 KO input DNA |
| GSM3752712 |
Breast cancer cell line, cSrcKO, 9327 KO input DNA |
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| This SubSeries is part of SuperSeries: |
| GSE130739 |
An ErbB2/c-Src axis drives mammary tumorigenesis through metabolically directed translational regulation of Polycomb Repressor Complex 2 |
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| Relations |
| BioProject |
PRJNA541244 |
| SRA |
SRP195513 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE130738_RAW.tar |
698.8 Mb |
(http)(custom) |
TAR (of BEDGRAPH) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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