TY - JOUR
T1 - NUAK2 localization in normal skin and its expression in a variety of skin tumors with YAP
AU - Al-Busani, Hind
AU - Al-Sobaihi, Saber
AU - Nojima, Kohei
AU - Tanemura, Atsushi
AU - Yaguchi, Tomonori
AU - Kawakami, Yutaka
AU - Matsumura, Hiroyuki
AU - Nishimura, Emi K.
AU - Yokozeki, Hiroo
AU - Namiki, Takeshi
N1 - Publisher Copyright:
© 2020 Japanese Society for Investigative Dermatology
PY - 2020/2
Y1 - 2020/2
N2 - 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.
AB - 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.
KW - Hippo pathway
KW - NUAK2
KW - PI3K pathway
KW - Skin tumors
KW - YAP
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UR - http://www.scopus.com/inward/citedby.url?scp=85078259579&partnerID=8YFLogxK
U2 - 10.1016/j.jdermsci.2020.01.008
DO - 10.1016/j.jdermsci.2020.01.008
M3 - Article
C2 - 32001115
AN - SCOPUS:85078259579
SN - 0923-1811
VL - 97
SP - 143
EP - 151
JO - Journal of Dermatological Science
JF - Journal of Dermatological Science
IS - 2
ER -
