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| Status |
Public on Aug 24, 2015 |
| Title |
Physical and functional CSL-p53 interactions underlie control of cancer stromal cell evolution [ChIP-seq] |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
Senescence of stromal fibroblasts has been linked to establishment of cancer associated fibroblasts (CAF) and aging-associated increase of tumors. However, in clinically occurring carcinomas, density and proliferation of CAFs are frequently increased rather than decreased. We previously showed that genetic deletion or down-modulation of the canonical Notch effector CSL/RBP-Jκ in skin dermal fibroblasts is sufficient for CAF activation with consequent development of multifocal keratinocyte tumors. We now show that CSL deletion or knockdown induces senescence of primary fibroblasts derived from dermis, oral mucosa, breast and lung. CSL functions in these cells as a constitutive direct repressor of multiple senescence- and CAF-effector genes. At the same time, it physically interacts with p53, repressing its activity, and p53 activation provides a failsafe mechanism against compromised CSL function. Concomitant loss of CSL and p53 overcomes fibroblast senescence, enhances expression of CAF effector genes and, in vivo, promotes tumour and stromal cell expansion. Together, the findings support a CAF activation/stromal evolution model under convergent CSL/p53 control.
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| |
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| Overall design |
Examination of genome-wide CSL binding sites in primary human dermal fibroblasts usinf two different antibodies against CSL
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| Contributor(s) |
Procopio MG, Lefort K, Ala U, Provero P |
| Citation(s) |
26302407, 31467287 |
| Submission date |
Jul 30, 2014 |
| Last update date |
Sep 11, 2019 |
| Contact name |
Paola Ostano |
| Organization name |
Fondazione Edo ed Elvo Tempia
|
| Street address |
via Malta 3
|
| City |
Biella |
| ZIP/Postal code |
13900 |
| Country |
Italy |
| |
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| Platforms (1) |
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
|
| Samples (3) |
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| This SubSeries is part of SuperSeries: |
| GSE65474 |
Physical and functional CSL-p53 interactions underlie control of cancer stromal cell evolution |
|
| Relations |
| BioProject |
PRJNA257105 |
| SRA |
SRP045116 |
