| First Author | Montagner A | Year | 2014 |
| Journal | EMBO Mol Med | Volume | 6 |
| Issue | 1 | Pages | 80-98 |
| PubMed ID | 24203162 | Mgi Jnum | J:232303 |
| Mgi Id | MGI:5776460 | Doi | 10.1002/emmm.201302666 |
| Citation | Montagner A, et al. (2014) Src is activated by the nuclear receptor peroxisome proliferator-activated receptor beta/delta in ultraviolet radiation-induced skin cancer. EMBO Mol Med 6(1):80-98 |
| abstractText | 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) beta/delta and the oncogene Src, which promotes the development of ultraviolet (UV)-induced skin cancer in mice. UV-induced PPARbeta/delta 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, PPARbeta/delta-null mice developed fewer and smaller skin tumours, and a PPARbeta/delta antagonist prevented UV-dependent Src stimulation. Furthermore, the expression of PPARbeta/delta 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 PPARbeta/delta and SRC and TGFbeta1 transcriptional levels. Taken together, these observations motivate the future evaluation of PPARbeta/delta modulators to attenuate the development of several epithelial cancers. |
