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| Status |
Public on Oct 05, 2016 |
| Title |
EPRS is a Critical Regulator of Cell Proliferation and Estrogen Signaling in ER+ Breast Cancer |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Aminoacyl tRNA synthetases (ARSs) are a class of enzymes with well-conserved housekeeping functions in cellular translation. Recent evidence suggests that ARS genes may participate in a wide array of cellular processes, and may contribute to the pathology of autoimmune disease, cancer, and other diseases. Several studies have suggested a role for the glutamyl prolyl tRNA synthetase (EPRS) in breast cancers, although none has demonstrated any underlying mechanism about how EPRS contributes to carcinogenesis. In this study, we identified EPRS as upregulated in estrogen receptor positive (ER+) human breast tumors in the TCGA and METABRIC cohorts, with copy number gains in nearly 50% of samples in both datasets. EPRS expression is associated with reduced overall survival in patients with ER+ tumors in TCGA and METABRIC datasets. EPRS expression was also associated with reduced distant relapse-free survival in patients treated with adjuvant tamoxifen monotherapy for five years, and EPRS-correlated genes were highly enriched for genes predictive of a poor response to tamoxifen. We demonstrated the necessity of EPRS for proliferation of tamoxifen-resistant ER+ breast cancer, but not ER- breast cancer cells. Transcriptomic profiling showed that EPRS regulated cell cycle and estrogen response genes. Finally, we constructed a causal gene network based on over 2500 ER+ breast tumor samples to build up an EPRS-estrogen signaling pathway. EPRS and its regulated estrogenic gene network may offer a promising alternative approach to target ER+ breast cancers that are refractory to current anti-estrogens.
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| |
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| Overall design |
Validation of EPRS Regulated Downstream Signature
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| |
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| Contributor(s) |
Katsyv I, Wang M, Song W, Zhou X, Zhao Y, Park S, Zhu J, Zhang B, Irie HY |
| Citation(s) |
27612429 |
| BioProject |
PRJNA318910 |
| |
| Submission date |
May 05, 2016 |
| Last update date |
May 15, 2019 |
| Contact name |
XIANXIAO ZHOU |
| E-mail(s) |
xianxiao.zhou@mssm.edu
|
| Phone |
2128248964
|
| Organization name |
Ichan School of Medicine at Mount Sinai
|
| Department |
Department of Genetics and Genomic Sciences
|
| Lab |
The Multiscale Network Modeling Laboratory
|
| Street address |
1470 Madison AVE
|
| City |
New York |
| State/province |
NY |
| ZIP/Postal code |
10029 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
|
| Samples (12)
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| Relations |
| SRA |
SRP073504 |
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