Convergent roles of ATF3 and CSL in chromatin control of cancer-associated fibroblast activation.

Détails

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Etat: Public
Version: Final published version
ID Serval
serval:BIB_BA934BF70A42
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Convergent roles of ATF3 and CSL in chromatin control of cancer-associated fibroblast activation.
Périodique
The Journal of Experimental Medicine
Auteur(s)
Kim D.E., Procopio M.G., Ghosh S., Jo S.H., Goruppi S., Magliozzi F., Bordignon P., Neel V., Angelino P., Dotto G.P.
ISSN
1540-9538 (Electronic)
ISSN-L
0022-1007
Statut éditorial
Publié
Date de publication
2017
Peer-reviewed
Oui
Volume
214
Numéro
8
Pages
2349-2368
Langue
anglais
Résumé
Cancer-associated fibroblasts (CAFs) are important for tumor initiation and promotion. CSL, a transcriptional repressor and Notch mediator, suppresses CAF activation. Like CSL, ATF3, a stress-responsive transcriptional repressor, is down-modulated in skin cancer stromal cells, and Atf3 knockout mice develop aggressive chemically induced skin tumors with enhanced CAF activation. Even at low basal levels, ATF3 converges with CSL in global chromatin control, binding to few genomic sites at a large distance from target genes. Consistent with this mode of regulation, deletion of one such site 2 Mb upstream of IL6 induces expression of the gene. Observed changes are of translational significance, as bromodomain and extra-terminal (BET) inhibitors, unlinking activated chromatin from basic transcription, counteract the effects of ATF3 or CSL loss on global gene expression and suppress CAF tumor-promoting properties in an in vivo model of squamous cancer-stromal cell expansion. Thus, ATF3 converges with CSL in negative control of CAF activation with epigenetic changes amenable to cancer- and stroma-focused intervention.

Pubmed
Web of science
Open Access
Oui
Création de la notice
08/09/2017 8:18
Dernière modification de la notice
20/08/2019 15:28
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