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| Status |
Public on Aug 25, 2020 |
| Title |
NOTCH1 gene amplification promotes expansion of Cancer Associated Fibroblast populations in human skin |
| Organism |
Homo sapiens |
| Experiment type |
Genome variation profiling by SNP array
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| Summary |
Cancer associated fibroblasts (CAFs) represent a key component of the tumor microenvironment. Possible genomic alterations in these cells remain a point of contention. The skin is constantly exposed to clastogenic insults, such as UVA light that can target directly the stromal compartment, therefore representing a relevant model to study. Here we report that CAFs from skin Squamous Cell Carcinoma (SCC) lesions display chromosomal alterations, with heterogeneous levels of NOTCH1 gene amplification that also occur, to a lesser extent, in dermal fibroblasts of apparently unaffected skin. The fraction of the latter cells harboring NOTCH1 gene amplification is expanded by chronic UVA exposure, which induces a DNA damage response (DDR) to which CAFs are resistant. The selective advantage conferred by NOTCH1 gene amplification and over-expression can be explained by NOTCH1 ability to block DDR-mediated growth arrest through competitive suppression of ATM-FOXO3a association and downstream signaling cascade. These findings are of translational significance as, in an orthotopic model of skin SCC, genetic or pharmacological inhibition of NOTCH1 activity suppresses cancer / stromal cells expansion. Thus, NOTCH1 amplification and increased expression contribute to CAFs evolution and are an attractive target for preventing cancer / stromal cell expansion.
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| Overall design |
Three independent CAF strains, at the 2nd passage after tumor dissociation, were analyzed by Comparative Genomic Hybridization (CGH).
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| Contributor(s) |
Bottoni G, Katarkar A, Clocchiatti A, Goruppi S, Bordignon P, Lazzaroni F, Gregnanin I, Ostano P, Neel V, Dotto GP |
| Citation(s) |
33046701 |
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| Submission date |
Apr 24, 2018 |
| Last update date |
Oct 27, 2020 |
| Contact name |
Paola Ostano |
| Organization name |
Fondazione Edo ed Elvo Tempia
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| Street address |
via Malta 3
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| City |
Biella |
| ZIP/Postal code |
13900 |
| Country |
Italy |
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| Platforms (1) |
| GPL16237 |
Agilent-030587 CCMC CGH plus SNP 180k Microarray |
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| Samples (3) |
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| This SubSeries is part of SuperSeries: |
| GSE113578 |
Dual role of CSL (RBP-Jk) and NOTCH1 in CAF |
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| Relations |
| BioProject |
PRJNA453141 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE113577_RAW.tar |
148.3 Mb |
(http)(custom) |
TAR (of TXT) |
| Processed data included within Sample table |
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