Nguyen et al. 2023 (PRJNA937159)
General Details
| Title | Rapamycin-Induced Feedback Activation of mRNA Translation in Pancreatic Cancer |
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| Organism | |
| Number of Samples | 6 |
| Release Date | 2023/02/21 00:00 |
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| Protocol Details |
Study Links
| GWIPS-viz | Trips-Viz |
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Repository Details
| SRA | SRP423678 |
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| ENA | SRP423678 |
| GEO | |
| BioProject | PRJNA937159 |
Publication
| Title | |
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| Authors | Nguyen TU,Hector H,Pederson EN,Lin J,Ouyang Z,Wendel HG,Singh K |
| Journal | Cancers |
| Publication Date | 2023 Feb 24 |
| Abstract | Pancreatic cancer cells adapt molecular mechanisms to activate the protein synthesis to support tumor growth. This study reports the mTOR inhibitor rapamycin's specific and genome-wide effect on mRNA translation. Using ribosome footprinting in pancreatic cancer cells that lack the expression of 4EBP1, we establish the effect of mTOR-S6-dependent mRNAs translation. Rapamycin inhibits the translation of a subset of mRNAs including p70-S6K and proteins involved in the cell cycle and cancer cell growth. In addition, we identify translation programs that are activated following mTOR inhibition. Interestingly, rapamycin treatment results in the translational activation of kinases that are involved in mTOR signaling such as p90-RSK1. We further show that phospho-AKT1 and phospho-eIF4E are upregulated following mTOR inhibition suggesting a feedback activation of translation by rapamycin. Next, targeting eIF4E and eIF4A-dependent translation by using specific eIF4A inhibitors in combination with rapamycin shows significant growth inhibition in pancreatic cancer cells. In short, we establish the specific effect of mTOR-S6 on translation in cells lacking 4EBP1 and show that mTOR inhibition leads to feedback activation of translation via AKT-RSK1-eIF4E signals. Therefore, targeting translation downstream of mTOR presents a more efficient therapeutic strategy in pancreatic cancer. |
| PMC | PMC10001351 |
| PMID | 36900235 |
| DOI |
| Run Accession | Study Accession | Scientific Name | Cell Line | Library Type | Treatment | GWIPS-viz | Trips-Viz | Reads | BAM | BigWig (F) | BigWig (R) | ||
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| SRR23563667 | PRJNA937159 | Homo sapiens | PANC1 |  |
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| SRR23563666 | PRJNA937159 | Homo sapiens | PANC1 | |
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| SRR23563665 | PRJNA937159 | Homo sapiens | PANC1 | |
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| SRR23563664 | PRJNA937159 | Homo sapiens | PANC1 | |
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| SRR23563663 | PRJNA937159 | Homo sapiens | PANC1 | |
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| SRR23563662 | PRJNA937159 | Homo sapiens | PANC1 | |
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| Run Accession | Study Accession | Scientific Name | Cell Line | Library Type | Treatment | GWIPS-viz | Trips-Viz | Reads | BAM | BigWig (F) | BigWig (R) |
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