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E-GEOD-65473 - Physical and functional CSL-p53 interactions underlie control of cancer stromal cell evolution [RNA-seq]

Status
Released on 24 August 2015, last updated on 29 August 2015
Organism
Homo sapiens
Samples (3)
Protocols (1)
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-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. 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.
Experiment type
RNA-seq of coding RNA 
Contacts
Cathrin Brisken, Csaba Laszlo, Dania Allabban, G P Dotto, Karine Lefort, Maria-Giuseppina Procopio, Melody Swartz, Paola Ostano, Paolo Provero, Pino Bordignon, Seung-Hee Jo, Ugo Ala, Vic Neel, Witek Kilarski
MINSEQE
Exp. designProtocolsVariablesProcessedSeq. reads
Files
Investigation descriptionE-GEOD-65473.idf.txt
Sample and data relationshipE-GEOD-65473.sdrf.txt
Processed data (1)E-GEOD-65473.processed.1.zip
Links