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| Status |
Public on Apr 05, 2023 |
| Title |
Escape From Oncogene-Induced Senescence is Controlled by POU2F2 and Memorized by Chromatin Scars [Expression] |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Although oncogene-induced senescence (OIS) is a potent tumor-suppressor mechanism, recent studies revealed that cells can escape from OIS with features of transformed cells. However, the mechanisms that promote OIS escape remain unclear, and evidence of post-senescent cells in human cancers is missing. Here, we unravel the regulatory mechanisms underlying OIS escape using dynamic multidimensional profiling. We demonstrate a critical role for AP1 and POU2F2 transcription factors for escape from OIS and identify ‘senescence-associated chromatin scars (SACS)’ as an epigenetic memory of OIS, detectable during colorectal cancer progression. POU2F2 levels are elevated already in precancerous lesions and as cells escape from OIS, and its expression and binding activity to cis-regulatory elements are associated with decreased patient survival. Our results support a model in which POU2F2 exploits a precoded enhancer landscape to promote senescence escape and reveal POU2F2 gene signatures and SACS as valuable biomarkers with diagnostic and prognostic potential.
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| Overall design |
RNA from each time-point (days 0, 8, 13 , 14, 18, 19, 21, 22, 23 , 25, 32, 45, 46, 50, 56) from GM21 fibroblasts undergoing escape from RAS-induced senescence was purified using the Macherey-Nagel Nucleospin RNA Plus XS kit according to the manufacturer’s instructions. 100 ng RNA per sample was analyzed using Affymetrix Human Transcriptome Arrays 2.0
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| Contributor(s) |
Zamudio RI, Stefa A, Nabuco JA, Vasilopoulos T, Simpson M, Doré G, Roux P, Galan MA, Chokshi RJ, Bischof O, Herbig U |
| Citation(s) |
37082139 |
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| Submission date |
Jun 08, 2022 |
| Last update date |
May 12, 2023 |
| Contact name |
Ricardo Iván Martínez Zamudio |
| E-mail(s) |
rm1238@rwjms.rutgers.edu
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| Organization name |
Rutgers Biomedical and Health Sciences | Rutgers-Robert Wood Johnson Medical School
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| Department |
Pharmacology
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| Lab |
Martínez Zamudio Lab
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| Street address |
675 Hoes Lane West
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| City |
Piscataway |
| State/province |
New Jersey |
| ZIP/Postal code |
08854 |
| Country |
USA |
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| Platforms (1) |
| GPL17586 |
[HTA-2_0] Affymetrix Human Transcriptome Array 2.0 [transcript (gene) version] |
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| Samples (34)
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| GSM6217436 |
GM21 fibroblasts, empty vector, biol rep 1, day 32 |
| GSM6217439 |
GM21 fibroblasts, empty vector, biol rep 1, day 56 |
| GSM6217443 |
GM21 fibroblasts, empty vector, biol rep 1, day 8 |
| GSM6217445 |
GM21 fibroblasts, RAS, biol rep 1, day 13 |
| GSM6217446 |
GM21 fibroblasts, RAS, biol rep 1, day 18 |
| GSM6217447 |
GM21 fibroblasts, RAS, biol rep 1, day 21 |
| GSM6217448 |
GM21 fibroblasts, RAS, biol rep 1, day 23 |
| GSM6217449 |
GM21 fibroblasts, RAS, biol rep 1, day 32 |
| GSM6217450 |
GM21 fibroblasts, RAS, biol rep 1, day 46 |
| GSM6217451 |
GM21 fibroblasts, RAS, biol rep 1, day 50 |
| GSM6217452 |
GM21 fibroblasts, RAS, biol rep 1, day 56 |
| GSM6217453 |
GM21 fibroblasts, RAS, biol rep 1, day 8 |
| GSM6217454 |
GM21 fibroblasts, empty vector, biol rep 2, day 32 |
| GSM6217455 |
GM21 fibroblasts, empty vector, biol rep 2, day 56 |
| GSM6217456 |
GM21 fibroblasts, empty vector, biol rep 2, day 8 |
| GSM6217457 |
GM21 fibroblasts, RAS, biol rep 2, day 14 |
| GSM6217458 |
GM21 fibroblasts, RAS, biol rep 2, day 19 |
| GSM6217459 |
GM21 fibroblasts, RAS, biol rep 2, day 21 |
| GSM6217460 |
GM21 fibroblasts, RAS, biol rep 2, day 22 |
| GSM6217461 |
GM21 fibroblasts, RAS, biol rep 2, day 25 |
| GSM6217462 |
GM21 fibroblasts, RAS, biol rep 2, day 32 |
| GSM6217463 |
GM21 fibroblasts, RAS, biol rep 2, day 45 |
| GSM6217464 |
GM21 fibroblasts, RAS, biol rep 2, day 56 |
| GSM6217465 |
GM21 fibroblasts, RAS, biol rep 2, day 8 |
| GSM6217466 |
GM21 fibroblasts, empty vector, biol rep 3, day 32 |
| GSM6217467 |
GM21 fibroblasts, empty vector, biol rep 3, day 56 |
| GSM6217468 |
GM21 fibroblasts, empty vector, biol rep 3, day 8 |
| GSM6217469 |
GM21 fibroblasts, RAS, biol rep 3, day 13 |
| GSM6217470 |
GM21 fibroblasts, RAS, biol rep 3, day 22 |
| GSM6217471 |
GM21 fibroblasts, RAS, biol rep 3, day 25 |
| GSM6217472 |
GM21 fibroblasts, RAS, biol rep 3, day 32 |
| GSM6217473 |
GM21 fibroblasts, RAS, biol rep 3, day 45 |
| GSM6217474 |
GM21 fibroblasts, RAS, biol rep 3, day 56 |
| GSM6217475 |
GM21 fibroblasts, RAS, biol rep 3, day 8 |
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| This SubSeries is part of SuperSeries: |
| GSE206496 |
Escape From Oncogene-Induced Senescence is Controlled by POU2F2 and Memorized by Chromatin Scars |
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| Relations |
| BioProject |
PRJNA847199 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE205692_RAW.tar |
801.7 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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