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GEO help: Mouse over screen elements for information. |
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| Status |
Public on May 25, 2021 |
| Title |
The integrated stress response is tumorigenic and constitutes a therapeutic liability in KRAS-driven lung cancer. |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
The integrated stress response (ISR) is an essential stress-support pathway increasingly recognized as a determinant of tumorigenesis. Here we demonstrate that ISR is pivotal in lung adenocarcinoma (LUAD) development, the most common histological type of lung cancer and a leading cause of cancer death worldwide. Increased phosphorylation of the translation initiation factor eIF2 (p-eIF2α), the focal point of ISR, is related to invasiveness, increased growth, and poor outcome in 928 LUAD patients. Dissection of ISR mechanisms in KRAS-driven lung tumorigenesis in mice demonstrated that p-eIF2α causes specific translational repression of dual specificity phosphatase 6 (DUSP6), resulting in increased phosphorylation of the extracellular signal-regulated kinase (p-ERK). Treatments with ISR inhibitors, including a memory-enhancing drug with limited toxicity, provides a novel therapeutic option for KRAS-driven lung cancer insofar as they substantially reduce tumor growth and prolong mouse survival. Our data provide a novel rationale for the implementation of ISR-based regimens in LUAD treatment.
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| Overall design |
RNA seq of eIF2αS/S and eIF2αA/A KRAS G12D Tumor Cells
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| Contributor(s) |
Koromilas AE, Le Quesne J, Larsson O, Topisirovic I, Hatzoglou M, Mann KK, Broggini M, Popper H, Teodósio A, Officer L, Ah-son N, Kazimierczak U, van Hoef V, Darini C, Krishnamoorthy J, Woodvine B, Wang S, Ghaddar N |
| Citation(s) |
34330898 |
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| Submission date |
Jul 27, 2020 |
| Last update date |
Aug 24, 2021 |
| Contact name |
Antonis Koromilas |
| Organization name |
1Lady Davis Institute for Medical Research, Sir Mortimer B. Davis-Jewish General Hospital
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| Street address |
3755 Chemin de la Côte-Sainte-Catherine
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| City |
Montreal |
| State/province |
Quebec |
| ZIP/Postal code |
H3T 1E2 |
| Country |
Canada |
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| Platforms (1) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
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| Samples (8)
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| Relations |
| BioProject |
PRJNA649008 |
| SRA |
SRP273789 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE155238_raw_counts.txt.gz |
321.9 Kb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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