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Targeting PRPK and TOPK for skin cancer prevention and therapy

Solar ultraviolet (sUV) irradiation is a major environmental carcinogen that can cause inflammation and skin cancer. The costs and morbidity associated with skin cancer are increasing, and therefore identifying molecules that can help prevent skin carcinogenesis is important. In this study, we ident...

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Autores principales: Roh, Eunmiri, Lee, Mee-Hyun, Zykova, Tatyana A., Zhu, Feng, Nadas, Janos, Kim, Hong-Gyum, Bae, Ki Beom, Li, Yan, Cho, Yong Yeon, Curiel-Lewandrowski, Clara, Einspahr, Janine, Dickinson, Sally E., Bode, Ann M., Dong, Zigang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6195829/
https://www.ncbi.nlm.nih.gov/pubmed/29904102
http://dx.doi.org/10.1038/s41388-018-0350-9
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author Roh, Eunmiri
Lee, Mee-Hyun
Zykova, Tatyana A.
Zhu, Feng
Nadas, Janos
Kim, Hong-Gyum
Bae, Ki Beom
Li, Yan
Cho, Yong Yeon
Curiel-Lewandrowski, Clara
Einspahr, Janine
Dickinson, Sally E.
Bode, Ann M.
Dong, Zigang
author_facet Roh, Eunmiri
Lee, Mee-Hyun
Zykova, Tatyana A.
Zhu, Feng
Nadas, Janos
Kim, Hong-Gyum
Bae, Ki Beom
Li, Yan
Cho, Yong Yeon
Curiel-Lewandrowski, Clara
Einspahr, Janine
Dickinson, Sally E.
Bode, Ann M.
Dong, Zigang
author_sort Roh, Eunmiri
collection PubMed
description Solar ultraviolet (sUV) irradiation is a major environmental carcinogen that can cause inflammation and skin cancer. The costs and morbidity associated with skin cancer are increasing, and therefore identifying molecules that can help prevent skin carcinogenesis is important. In this study, we identified the p53-related protein kinase (PRPK) as a novel oncogenic protein that is phosphorylated by the T-LAK cell-originated protein kinase (TOPK). Knockdown of TOPK inhibited PRPK phosphorylation and conferred resistance to solar simulated light (SSL)-induced skin carcinogenesis in mouse models. In the clinic, acute SSL irradiation significantly increased epidermal thickness as well as total protein and phosphorylation levels of TOPK and PRPK in human skin tissues. We identified two PRPK inhibitors, FDA-approved rocuronium bromide (Zemuron®) or betamethasone 17-valerate (Betaderm®) that could attenuate TOPK-dependent PRPK signaling. Importantly, topical application of either rocuronium bromide or betamethasone decreased SSL-induced epidermal hyperplasia, neovascularization and cutaneous squamous cell carcinoma (cSCC) development in SKH1 (Crl: SKH1-Hr(hr)) hairless mice by inhibiting PRPK activation, and also reduced expression of the proliferation and oncogenesis markers, COX-2, cyclin D1 and MMP-9. This study is the first to demonstrate that targeting PRPK could be useful against sUV-induced cSCC development.
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spelling pubmed-61958292018-12-14 Targeting PRPK and TOPK for skin cancer prevention and therapy Roh, Eunmiri Lee, Mee-Hyun Zykova, Tatyana A. Zhu, Feng Nadas, Janos Kim, Hong-Gyum Bae, Ki Beom Li, Yan Cho, Yong Yeon Curiel-Lewandrowski, Clara Einspahr, Janine Dickinson, Sally E. Bode, Ann M. Dong, Zigang Oncogene Article Solar ultraviolet (sUV) irradiation is a major environmental carcinogen that can cause inflammation and skin cancer. The costs and morbidity associated with skin cancer are increasing, and therefore identifying molecules that can help prevent skin carcinogenesis is important. In this study, we identified the p53-related protein kinase (PRPK) as a novel oncogenic protein that is phosphorylated by the T-LAK cell-originated protein kinase (TOPK). Knockdown of TOPK inhibited PRPK phosphorylation and conferred resistance to solar simulated light (SSL)-induced skin carcinogenesis in mouse models. In the clinic, acute SSL irradiation significantly increased epidermal thickness as well as total protein and phosphorylation levels of TOPK and PRPK in human skin tissues. We identified two PRPK inhibitors, FDA-approved rocuronium bromide (Zemuron®) or betamethasone 17-valerate (Betaderm®) that could attenuate TOPK-dependent PRPK signaling. Importantly, topical application of either rocuronium bromide or betamethasone decreased SSL-induced epidermal hyperplasia, neovascularization and cutaneous squamous cell carcinoma (cSCC) development in SKH1 (Crl: SKH1-Hr(hr)) hairless mice by inhibiting PRPK activation, and also reduced expression of the proliferation and oncogenesis markers, COX-2, cyclin D1 and MMP-9. This study is the first to demonstrate that targeting PRPK could be useful against sUV-induced cSCC development. 2018-06-14 2018-10 /pmc/articles/PMC6195829/ /pubmed/29904102 http://dx.doi.org/10.1038/s41388-018-0350-9 Text en Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Roh, Eunmiri
Lee, Mee-Hyun
Zykova, Tatyana A.
Zhu, Feng
Nadas, Janos
Kim, Hong-Gyum
Bae, Ki Beom
Li, Yan
Cho, Yong Yeon
Curiel-Lewandrowski, Clara
Einspahr, Janine
Dickinson, Sally E.
Bode, Ann M.
Dong, Zigang
Targeting PRPK and TOPK for skin cancer prevention and therapy
title Targeting PRPK and TOPK for skin cancer prevention and therapy
title_full Targeting PRPK and TOPK for skin cancer prevention and therapy
title_fullStr Targeting PRPK and TOPK for skin cancer prevention and therapy
title_full_unstemmed Targeting PRPK and TOPK for skin cancer prevention and therapy
title_short Targeting PRPK and TOPK for skin cancer prevention and therapy
title_sort targeting prpk and topk for skin cancer prevention and therapy
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6195829/
https://www.ncbi.nlm.nih.gov/pubmed/29904102
http://dx.doi.org/10.1038/s41388-018-0350-9
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