Src is activated by the nuclear receptor peroxisome proliferator-activated receptor β/δ in ultraviolet radiation-induced skin cancer.

Détails

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Etat: Public
Version: de l'auteur
ID Serval
serval:BIB_61D2EDA76529
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Src is activated by the nuclear receptor peroxisome proliferator-activated receptor β/δ in ultraviolet radiation-induced skin cancer.
Périodique
EMBO Molecular Medicine
Auteur(s)
Montagner A., Delgado M.B., Tallichet-Blanc C., Chan J.S., Sng M.K., Mottaz H., Degueurce G., Lippi Y., Moret C., Baruchet M., Antsiferova M., Werner S., Hohl D., Saati T.A., Farmer P.J., Tan N.S., Michalik L., Wahli W.
ISSN
1757-4684 (Electronic)
ISSN-L
1757-4676
Statut éditorial
Publié
Date de publication
2014
Volume
6
Numéro
1
Pages
80-98
Langue
anglais
Résumé
Although non-melanoma skin cancer (NMSC) is the most common human cancer and its incidence continues to rise worldwide, the mechanisms underlying its development remain incompletely understood. Here, we unveil a cascade of events involving peroxisome proliferator-activated receptor (PPAR) β/δ and the oncogene Src, which promotes the development of ultraviolet (UV)-induced skin cancer in mice. UV-induced PPARβ/δ activity, which directly stimulated Src expression, increased Src kinase activity and enhanced the EGFR/Erk1/2 signalling pathway, resulting in increased epithelial-to-mesenchymal transition (EMT) marker expression. Consistent with these observations, PPARβ/δ-null mice developed fewer and smaller skin tumours, and a PPARβ/δ antagonist prevented UV-dependent Src stimulation. Furthermore, the expression of PPARβ/δ positively correlated with the expression of SRC and EMT markers in human skin squamous cell carcinoma (SCC), and critically, linear models applied to several human epithelial cancers revealed an interaction between PPARβ/δ and SRC and TGFβ1 transcriptional levels. Taken together, these observations motivate the future evaluation of PPARβ/δ modulators to attenuate the development of several epithelial cancers.
Pubmed
Web of science
Open Access
Oui
Création de la notice
15/05/2014 9:24
Dernière modification de la notice
20/08/2019 15:18
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