Targeting PRPK and TOPK for skin cancer prevention and therapy

Eunmiri Roh, Mee Hyun Lee, Tatyana A. Zykova, Feng Zhu, Janos Nadas, Hong Gyum Kim, Ki Beom Bae, Yan Li, Yong Yeon Cho, Clara N Curiel, Janine G Einspahr, Sally E Dickinson, Ann M. Bode, Zigang Dong

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

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-Hrhr) 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.

Original languageEnglish (US)
Pages (from-to)1-15
Number of pages15
JournalOncogene
DOIs
StateAccepted/In press - Jun 14 2018

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Lymphokine-Activated Killer Cells
Skin Neoplasms
Protein Kinases
Skin
Carcinogenesis
Therapeutics
Light
Squamous Cell Carcinoma
Betamethasone Valerate
Phosphorylation
Environmental Carcinogens
Hairless Mouse
Betamethasone
Cyclin D1
Protein Kinase Inhibitors
Matrix Metalloproteinases
Hyperplasia
Proteins
Inflammation
Morbidity

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this

Roh, E., Lee, M. H., Zykova, T. A., Zhu, F., Nadas, J., Kim, H. G., ... Dong, Z. (Accepted/In press). Targeting PRPK and TOPK for skin cancer prevention and therapy. Oncogene, 1-15. https://doi.org/10.1038/s41388-018-0350-9

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, Clara N; Einspahr, Janine G; Dickinson, Sally E; Bode, Ann M.; Dong, Zigang.

In: Oncogene, 14.06.2018, p. 1-15.

Research output: Contribution to journalArticle

Roh, E, Lee, MH, Zykova, TA, Zhu, F, Nadas, J, Kim, HG, Bae, KB, Li, Y, Cho, YY, Curiel, CN, Einspahr, JG, Dickinson, SE, Bode, AM & Dong, Z 2018, 'Targeting PRPK and TOPK for skin cancer prevention and therapy', Oncogene, pp. 1-15. https://doi.org/10.1038/s41388-018-0350-9
Roh E, Lee MH, Zykova TA, Zhu F, Nadas J, Kim HG et al. Targeting PRPK and TOPK for skin cancer prevention and therapy. Oncogene. 2018 Jun 14;1-15. https://doi.org/10.1038/s41388-018-0350-9
Roh, Eunmiri ; Lee, Mee Hyun ; Zykova, Tatyana A. ; Zhu, Feng ; Nadas, Janos ; Kim, Hong Gyum ; Bae, Ki Beom ; Li, Yan ; Cho, Yong Yeon ; Curiel, Clara N ; Einspahr, Janine G ; Dickinson, Sally E ; Bode, Ann M. ; Dong, Zigang. / Targeting PRPK and TOPK for skin cancer prevention and therapy. In: Oncogene. 2018 ; pp. 1-15.
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AU - Dong, Zigang

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