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Series GSE65473 Query DataSets for GSE65473
Status Public on Aug 24, 2015
Title Physical and functional CSL-p53 interactions underlie control of cancer stromal cell evolution [RNA-seq]
Organism Homo sapiens
Experiment type Expression 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.
Overall design Human Dermal Fibroblasts were transfected with two different siRNA against CSL in parallel with a control siRNA. Total RNA was extracted 3 days post-transfection, followed by RNA-Seq analysis.
Contributor(s) Procopio M, Laszlo C, Allabban D, Bordignon P, Jo S, Ostano P, Ala U, Provero P, Neel V, Kilarski W, Swartz M, Brisken C, Lefort K, Dotto GP
Citation(s) 26302407
Submission date Jan 30, 2015
Last update date May 15, 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
Platforms (1)
GPL16791 Illumina HiSeq 2500 (Homo sapiens)
Samples (3)
GSM1598162 HDF si-CTRL
GSM1598163 HDF si-CSL_1
GSM1598164 HDF si-CSL_2
This SubSeries is part of SuperSeries:
GSE65474 Physical and functional CSL-p53 interactions underlie control of cancer stromal cell evolution
BioProject PRJNA274128
SRA SRP052998

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Supplementary file Size Download File type/resource
GSE65473_RAW.tar 290.0 Kb (http)(custom) TAR (of TXT)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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