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

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Version: author
Serval ID
serval:BIB_61D2EDA76529
Type
Article: article from journal or magazin.
Collection
Publications
Title
Src is activated by the nuclear receptor peroxisome proliferator-activated receptor β/δ in ultraviolet radiation-induced skin cancer.
Journal
EMBO Molecular Medicine
Author(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
Publication state
Published
Issued date
2014
Volume
6
Number
1
Pages
80-98
Language
english
Abstract
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
Yes
Create date
15/05/2014 9:24
Last modification date
20/08/2019 15:18
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