NUAK2 localization in normal skin and its expression in a variety of skin tumors with YAP
NUAK2 localization in normal skin and its expression in a variety of skin tumors with YAP
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DOI：
10.1016/j.jdermsci.2020.01.008
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发表时间：
2020-02-01
影响因子：
4.6
通讯作者：
Namiki, Takeshi
中科院分区：
文献类型：
--
作者：
Al-Busani, Hind;Al-Sobaihi, Saber;Namiki, Takeshi
背景：NUAK 2是参与包括黑色素瘤在内的多种类型癌症的发生的关键基因。然而，NUAK 2在正常皮肤和各种皮肤肿瘤中的表达模式至今尚未完全阐明。目的：阐明NUAK 2在正常皮肤中的表达分布和定位，并表征NUAK 2和雅普在各种皮肤肿瘤中的表达模式。在本研究中，我们通过开发一种新的NUAK 2-特异性单克隆抗体，并使用其来确定NUAK 2在正常皮肤和155例各种类型的皮肤肿瘤中的表达模式，包括乳房外佩吉特病（EMPD），鳞状细胞癌（SCC）、Bowen病（BD）、光化性角化病（AK）、基底细胞癌（BCC）和血管肉瘤（AS）。结果：NUAK 2在EMPD、SCC、BD、AK、BCC和AS中的表达频率较高。EMPD中p-Akt的表达与肿瘤大小呈正相关（P = 0.001）。重要的是，NUAK 2的表达与雅普在SCC（P = 0.012）和BD（P = 0.009）显著相关。结论：我们的研究结果表明，YAP-NUAK 2轴在SCC和BD的肿瘤发生中具有至关重要的作用，靶向YAP-NUAK 2轴的治疗方法可能是一种有效的治疗方法，包括SCC和BD。(C)2020日本皮肤病研究学会。Elsevier B. V.出版，保留所有权利。
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. (C) 2020 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.