NUAK2 localization in normal skin and its expression in a variety of skin tumors with YAP

Hind Al-Busani, Saber Al-Sobaihi, Kohei Nojima, Atsushi Tanemura, Tomonori Yaguchi, Yutaka Kawakami, Hiroyuki Matsumura, Emi K. Nishimura, Hiroo Yokozeki, Takeshi Namiki

Research output: Contribution to journalArticle

Abstract

Background: NUAK2 is a critical gene that participates in the carcinogenesis of various types of cancers including melanomas. However, the expression patterns of NUAK2 in normal skin and in various types of skin tumors have not been fully elucidated to date. Objectives: To elucidate the distribution and localization of NUAK2 expression in normal skin, and characterize the expression patterns of NUAK2 and YAP in various types of skin tumors. Methods: In this study, we characterized the expression of NUAK2 in tissues by developing a novel NUAK2-specific monoclonal antibody and using that to determine NUAK2 expression patterns in normal skin and in 155 cases of various types of skin tumors, including extramammary Paget's disease (EMPD), squamous cell carcinoma (SCC), Bowen's disease (BD), actinic keratosis (AK), basal cell carcinoma (BCC) and angiosarcoma (AS). Further, we analyzed the expression patterns of YAP and p-Akt in those tumors. Results: Our analyses revealed that NUAK2 is expressed at high frequencies in EMPD, SCC, BD, AK, BCC and AS. The expression of p-Akt was positively correlated with tumor size in EMPD (P = 0.001). Importantly, the expression of NUAK2 was significantly correlated with YAP in SCC (P = 0.012) and in BD (P = 0.009). Conclusions: Our results suggest that the YAP-NUAK2 axis has critical importance in the tumorigenesis of SCC and BD, and that therapeutic modalities targeting the YAP-NUAK2 axis may be an effective approach against skin tumors including SCC and BD.

Original languageEnglish
Pages (from-to)143-151
Number of pages9
JournalJournal of Dermatological Science
Volume97
Issue number2
DOIs
Publication statusPublished - 2020 Feb

Keywords

  • Hippo pathway
  • NUAK2
  • PI3K pathway
  • Skin tumors
  • YAP

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology

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  • Cite this

    Al-Busani, H., Al-Sobaihi, S., Nojima, K., Tanemura, A., Yaguchi, T., Kawakami, Y., Matsumura, H., Nishimura, E. K., Yokozeki, H., & Namiki, T. (2020). NUAK2 localization in normal skin and its expression in a variety of skin tumors with YAP. Journal of Dermatological Science, 97(2), 143-151. https://doi.org/10.1016/j.jdermsci.2020.01.008