github link
Accession IconGSE59847

Global changes in gene expression in human dermal fibroblasts after CSL silencing

Organism Icon Homo sapiens
Sample Icon 3 Downloadable Samples
Technology Badge Icon Affymetrix Human Genome U133A 2.0 Array (hgu133a2)

Submitter Supplied Information

Description
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-J-kappa 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, with p53 activation providing a failsafe mechanism against compromised CSL function. Concomitant loss of CSL and p53 overcomes fibroblasts senescence, enhances CAF effector gene expression and, in vivo, promotes stromal and cancer cell expansion. Together, these findings support a CAF activation/stromal evolution model under convergent CSL/p53 control.
PubMed ID
Total Samples
3
Submitter’s Institution
Alternate Accession IDs

Samples

Show of 0 Total Samples
Filter
Add/Remove
Accession Code
Title
Specimen part
Processing Information
Additional Metadata
No rows found
Loading...