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Title: Src is activated by the nuclear receptor peroxisome proliferator-activated receptor β/δ in ultraviolet radiation-induced skin cancer
Authors: Chan, Jeremy Soon Kiat
Montagner, Alexandra
Tallichet-Blanc, Corinne
Mottaz, Hélène
Degueurce, Gwendoline
Lippi, Yannick
Moret, Catherine
Baruchet, Michael
Antsiferova, Maria
Werner, Sabine
Hohl, Daniel
Al Saati, Talal
Michalik, Liliane
Wahli, Walter
Delgado, Maria B.
Sng, Ming K.
Farmer, Pierre J.
Tan, Nguan S.
Keywords: DRNTU::Science::Medicine
Issue Date: 2013
Source: Montagner, A., Delgado, M. B., Tallichet-Blanc, C., Chan, J. S. K., Sng, M. K., Mottaz, H., Degueurce, G., Lippi, Y., Moret, C., Baruchet, M., Antsiferova, M., Werner, S., Hohl, D., Al Saati, T., Farmer, P. J., Tan, N. S., Michalik, L.,& Wahli, W. (2014). Src is activated by the nuclear receptor peroxisome proliferator-activated receptor β/δ in ultraviolet radiation-induced skin cancer. EMBO Molecular Medicine, 6(1), 80-98.
Series/Report no.: EMBO molecular medicine
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.
ISSN: 1757-4676
DOI: 10.1002/emmm.201302666
Rights: © 2013 The Authors. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:LKCMedicine Journal Articles

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