Transcriptomics

Dataset Information

0

Dual role of CSL (RBP-Jk) and NOTCH1 in cancer-associated fibroblast genome stability and expansion [RNA-seq]


ABSTRACT: Genomic instability is a hallmark of cancer. Whether or not it also occurs in cancer-associated fibroblasts (CAFs) is a question of importance for the cancer/stromal cell co-evolution process. We find that DNA damage, telomere shortening and chromosome fusions occur at early times of CAF activation, as triggered by silencing of the CSL/RBP-J-κ gene in primary human dermal fibroblasts (HDFs) from multiple individuals. Similar alterations occur in skin Squamous Cell Carcinoma (SCC) - derived CAFs, in which CSL is down-modulated, versus HDFs from unaffected skin of the same patients. Mechanistically, CSL is part of a telomere protective complex with UPF1, KU70, and KU80 proteins, which fail to bind to telomeres in the absence of CSL. In CAFs, persistent genomic instability is associated with frequent amplification and overexpression of NOTCH1 gene, which is required to suppress DNA damage-induced ATM/P53 activation and growth arrest. These findings are of translational significance as, in an orthotopic model of skin SCC, genetic or pharmacological suppression of NOTCH1 activity suppresses cancer/stromal cell proliferation and expansion.

ORGANISM(S): Homo sapiens

PROVIDER: GSE113542 | GEO | 2019/09/11

REPOSITORIES: GEO

Dataset's files

Source:
Action DRS
Other
Items per page:
1 - 1 of 1

Similar Datasets

2020-08-25 | GSE113577 | GEO
2017-06-30 | GSE81405 | GEO
2017-06-30 | GSE81404 | GEO
2017-06-30 | GSE81403 | GEO
2018-08-28 | GSE107319 | GEO
2018-08-28 | GSE107320 | GEO
2015-08-24 | E-GEOD-59942 | biostudies-arrayexpress
2015-08-24 | E-GEOD-65473 | biostudies-arrayexpress
2017-12-15 | GSE102761 | GEO
2017-12-15 | GSE102762 | GEO