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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Feb 28, 2012 |
| Title |
The translational landscape of mTOR signaling steers cancer initiation and metastasis |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
The mammalian target of rapamycin (mTOR) kinase is a master regulator of protein synthesis that couples nutrient sensing to cell growth and cancer. However, the downstream translationally regulated nodes of gene expression that may direct cancer development are poorly characterized. Employing ribosome profiling we uncover specialized translation of the prostate cancer genome by oncogenic mTOR signaling, revealing a remarkably specific repertoire of genes involved in cell proliferation, metabolism, and invasion. We extend these findings by functionally characterizing a class of translationally controlled pro-invasion mRNAs that we show direct prostate cancer invasion and metastasis downstream of oncogenic mTOR signaling. We further develop a clinically relevant ATP site inhibitor of mTOR, INK128, which reprograms this gene expression signature with therapeutic benefit for prostate cancer metastasis, for which there is presently no cure. Together, these findings significantly extend our understanding of how the “cancerous” translation machinery steers specific cancer cell behaviors and may be therapeutically targeted.
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| Overall design |
Examination of mRNA translation in human prostate cancer upon differential inhibition of the mTOR signaling pathway.
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| Contributor(s) |
Hsieh AC, Liu Y, Edlind MP, Ingolia NT, Janes MR, Sher A, Shi EY, Stumpf CR, Christensen C, Bonham M, Wang S, Ren P, Martin M, Jessen K, Feldman ME, Weissman JS, Shokat KM, Rommel C, Ruggero D |
| Citation(s) |
22367541 |
| Submission date |
Feb 01, 2012 |
| Last update date |
May 15, 2019 |
| Contact name |
Andrew Caleb Hsieh |
| E-mail(s) |
andrew.hsieh@ucsf.edu
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| Phone |
415-514-4827
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| Fax |
415-514-4826
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| Organization name |
UCSF
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| Department |
Urology
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| Lab |
Davide Ruggero
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| Street address |
1450 3rd Street, HD Rm 319
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| City |
San Francisco |
| State/province |
CA |
| ZIP/Postal code |
94158 |
| Country |
USA |
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| Platforms (1) |
| GPL9115 |
Illumina Genome Analyzer II (Homo sapiens) |
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| Samples (12)
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| GSM869036 |
mRNA-seq for vehicle treated PC3 cells, replicate #1. |
| GSM869037 |
Footprint for vehicle treated PC3 cells, replicate #1. |
| GSM869038 |
mRNA-seq for rapamycin treated PC3 cells, replicate #1. |
| GSM869039 |
Footprint for rapamycin treated PC3 cells, replicate #1. |
| GSM869040 |
mRNA-seq for PP242 treated PC3 cells, replicate #1. |
| GSM869041 |
Footprint for PP242 treated PC3 cells, replicate #1. |
| GSM869042 |
mRNA-seq for vehicle treated PC3 cells, replicate #2. |
| GSM869043 |
Footprint for vehicle treated PC3 cells, replicate #2. |
| GSM869044 |
mRNA-seq for rapamycin treated PC3 cells, replicate #2. |
| GSM869045 |
Footprint for rapamycin treated PC3 cells, replicate #2. |
| GSM869046 |
mRNA-seq for PP242 treated PC3 cells, replicate #2. |
| GSM869047 |
Footprint for PP242 treated PC3 cells, replicate #2. |
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| Relations |
| SRA |
SRP010679 |
| BioProject |
PRJNA152347 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE35469_RAW.tar |
1.5 Mb |
(http)(custom) |
TAR (of TXT) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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