The ULK3 Kinase Is Critical for Convergent Control of Cancer-Associated Fibroblast Activation by CSL and GLI.

Détails

Ressource 1Télécharger: 1-s2.0-S2211124717311737-main.pdf (4202.65 [Ko])
Etat: Public
Version: Final published version
ID Serval
serval:BIB_92CAEAD2DD42
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
The ULK3 Kinase Is Critical for Convergent Control of Cancer-Associated Fibroblast Activation by CSL and GLI.
Périodique
Cell reports
Auteur(s)
Goruppi S., Procopio M.G., Jo S., Clocchiatti A., Neel V., Dotto G.P.
ISSN
2211-1247 (Electronic)
Statut éditorial
Publié
Date de publication
05/09/2017
Peer-reviewed
Oui
Volume
20
Numéro
10
Pages
2468-2479
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: ppublish
Résumé
The connection between signaling pathways activating cancer-associated fibroblasts (CAFs) remains to be determined. Metabolic alterations linked to autophagy have also been implicated in CAF activation. CSL/RBPJ, a transcriptional repressor that mediates Notch signaling, suppresses the gene expression program(s), leading to stromal senescence and CAF activation. Deregulated GLI signaling can also contribute to CAF conversion. Here, we report that compromised CSL function depends on GLI activation for conversion of human dermal fibroblasts into CAFs, separately from cellular senescence. Decreased CSL upregulates the expression of the ULK3 kinase, which binds and activates GLI2. Increased ULK3 also induces autophagy, which is unlinked from GLI and CAF activation. ULK3 upregulation occurs in the CAFs of several tumor types, and ULK3 silencing suppresses the tumor-enhancing properties of these cells. Thus, ULK3 links two key signaling pathways involved in CAF conversion and is an attractive target for stroma-focused anti-cancer intervention.
Mots-clé
Animals, Autophagy/physiology, Cancer-Associated Fibroblasts/metabolism, Female, Fibroblasts/metabolism, Fluorescent Antibody Technique, Humans, Immunoglobulin J Recombination Signal Sequence-Binding Protein/metabolism, Mice, Protein-Serine-Threonine Kinases/genetics, Protein-Serine-Threonine Kinases/metabolism, Signal Transduction/genetics, Signal Transduction/physiology, Zinc Finger Protein GLI1/genetics, Zinc Finger Protein GLI1/metabolism, CAF, CSL/RBPJ, GLI, SCC, ULK3, autophagy, cancer stroma, cancer-associated fibroblast, squamous cell carcinoma, tumor microenvironment
Pubmed
Web of science
Open Access
Oui
Création de la notice
29/09/2017 8:42
Dernière modification de la notice
20/08/2019 14:55
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