Sunlight UV-induced skin cancer relies upon activation of the p38α signaling pathway

Kangdong Liu, Donghoon Yu, Yong Yeon Cho, Ann M. Bode, Weiya Ma, Ke Yao, Shengqing Li, Jixia Li, G. Tim Bowden, Zigang Dong, Ziming Dong

Research output: Contribution to journalArticlepeer-review

45 Scopus citations

Abstract

The activation of cellular signal transduction pathways by solar ultraviolet (SUV) irradiation plays a vital role in skin tumorigenesis. Although many pathways have been studied using pure ultraviolet A (UVA) or ultraviolet B (UVB) irradiation, the signaling pathways induced by SUV (i.e., sunlight) are not understood well enough to permit improvements for prevention, prognosis, and treatment. Here, we report parallel protein kinase array studies aimed at determining the dominant signaling pathway involved in SUV irradiation. Our results indicated that the p38-related signal transduction pathway was dramatically affected by SUV irradiation. SUV (60 kJ UVA/m2/3.6 kJ UVB/m2) irradiation stimulates phosphorylation of p38α (MAPK14) by 5.78-fold, MSK2 (RPS6KA4) by 6.38-fold, and HSP27 (HSPB1) by 34.56-fold compared with untreated controls. By investigating the tumorigenic role of SUV-induced signal transduction in wild-type and p38 dominant-negative (p38 DN) mice, we found that p38 blockade yielded fewer and smaller tumors. These results establish that p38 signaling is critical for SUV-induced skin carcinogenesis.

Original languageEnglish (US)
Pages (from-to)2181-2188
Number of pages8
JournalCancer Research
Volume73
Issue number7
DOIs
StatePublished - Apr 1 2013

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