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Fyn is a redox sensor involved in solar ultraviolet light-induced signal transduction in skin carcinogenesis

Oncogene volume 35, pages 4091–4101 (2016)Cite this article

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Abstract

Solar ultraviolet (UV) light is a major etiological factor in skin carcinogenesis, with solar UV-stimulated signal transduction inducing pathological changes and skin damage. The primary sensor of solar UV-induced cellular signaling has not been identified. We use an experimental system of solar simulated light (SSL) to mimic solar UV and we demonstrate that Fyn is a primary redox sensor involved in SSL-induced signal transduction. Reactive oxygen species (ROS) generated by SSL exposure directly oxidize Cys488 of Fyn, resulting in increased Fyn kinase activity. Fyn oxidation was increased in mouse skin after SSL exposure and Fyn-knockout mice formed larger and more tumors compared with Fyn wild-type mice when exposed to SSL for an extended period of time. Murine embryonic fibroblasts (MEFs) lacking Fyn and cells in which Fyn expression was knocked down were resistant to SSL-induced apoptosis. Furthermore, cells expressing mutant Fyn (C448A) were resistant to SSL-induced apoptosis. These findings suggest that Fyn acts as a regulatory nexus between solar UV, ROS and signal transduction during skin carcinogenesis.

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Acknowledgements

This work was supported by The Hormel Foundation and National Institutes of Health grants to ZD (CA077646, CA027502, CA166011, CA172457 and R37CA081064), the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (F00044) and the Leap Research Program through the National Research Foundation, Ministry of Science, ICT and Future Planning, Republic of Korea (2015R1A2A1A10053567).

Author contributions

AMB, KWL, ZD, SD, DA, GTB, JE, SS and CC designed the experiments. JEK, ER, MHL, CP and YYC performed the research experiments. DHY, DJK, TGL and SKJ analyzed data. JEK and AMB wrote the paper.

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Author notes

  1. J-E Kim and E Roh: These authors contributed equally to this work.

Authors and Affiliations

  1. The Hormel Institute, University of Minnesota, Austin, MN, USA

    J-E Kim, E Roh, M H Lee, D H Yu, D J Kim, T-G Lim, S K Jung, C Peng, Y-Y Cho, A M Bode & Z Dong

  2. Department of Agricultural Biotechnology, Seoul National University, Seoul, Republic of Korea

    J-E Kim, T-G Lim, S K Jung & K W Lee

  3. Advanced Institutes of Convergence Technology, Seoul National University, Suwon, Gyeonggi-do, Republic of Korea

    J-E Kim, T-G Lim & K W Lee

  4. China-US Hormel Cancer Institute, Zhenzhou, Henan, China

    M H Lee

  5. Division of Strategic Food Research, Korea Food Research Institute, Seongnam-si, Gyeonggi-do, Republic of Korea

    T-G Lim & S K Jung

  6. College of Pharmacy, The Catholic University of Korea, Bucheon-si, Gyeonggi-do, Republic of Korea

    Y-Y Cho

  7. University of Arizona Cancer Center, Tucson, AZ, USA

    S Dickinson, D Alberts, G T Bowden, J Einspahr, S P Stratton & C Curiel-Lewandrowski

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  1. J-E Kim
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Correspondence to K W Lee or Z Dong.

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Kim, JE., Roh, E., Lee, M. et al. Fyn is a redox sensor involved in solar ultraviolet light-induced signal transduction in skin carcinogenesis. Oncogene 35, 4091–4101 (2016). https://doi.org/10.1038/onc.2015.471

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