PCTAIRE1/CDK16/PCTK1 is overexpressed in cutaneous squamous cell carcinoma and regulates p27 stability and cell cycle. Issue 2 (May 2017)

• Record Type: Journal Article
• Authors: Yanagi, Teruki; Hata, Hiroo; Mizuno, Eri; Kitamura, Shinya; Imafuku, Keisuke; Nakazato, Shinichi; Wang, Lei; Nishihara, Hiroshi; Tanaka, Shinya; Shimizu, Hiroshi
• Is Part Of: Journal of dermatological science. Volume 86:Issue 2(2017:May)
• Page Start: 149
• Page End: 157
• Publication Date: 2017-05
• Subjects: Cdk cyclin-dependent kinase -- Dox doxycycline -- PI propidium iodide -- SCC squamous cell carcinoma; Cutaneous squamous cell carcinoma -- Cyclin dependent kinase -- p27 -- Cell cycle; Dermatology -- Periodicals; Skin Diseases -- Periodicals; Dermatologie -- Périodiques; 616.5005
• DOI: 10.1016/j.jdermsci.2017.02.281
• Languages: English
• ISSNs: 0923-1811

Abstract

Highlights: The tumorigenic function of PCTAIRE1 in cutaneous SCC remains unclear. Pathological increases in PCTAIRE1 expression occur in cutaneous SCC. PCTAIRE1 knockdown restores p27 protein expression and suppresses SCC tumor growth. The depletion of PCTAIRE1 was found to lead to the down-regulation of c-Myc. PCTAIRE1 is required for normal cell division in cutaneous SCC cells. Abstract: Background: PCTAIRE1 (also known as cyclin-dependent kinase 16 (Cdk16) and PCTK1) is a Cdk family protein that has been implicated in spermatogenesis. We recently revealed the function of PCTAIRE1 in the tumorigenesis of malignancies, including breast and prostate cancers; however, the tumorigenic function of PCTAIRE1 in cutaneous squamous cell carcinoma (SCC) remains unclear. Objective: In this study, we investigated the role of PCTAIRE1 in the tumorigenesis of cutaneous SCCs. Methods and results: In cutaneous/oral SCC A431, DJM-1, HSC-3 cells, PCTAIRE1 gene-knockdown was found to diminish cell proliferation as assessed by cell counting and clonogenic assays. FACS analyses of annexin V-PI staining and DNA content showed PCTAIRE1 knockdown to cause G2/M arrest followed by apoptosis. The depletion of PCTAIRE1 was found to lead to the accumulation of tumor suppressor p27 and down-regulation of c-Myc. In tumor xenografts of A431 cells, the conditional knockdown of PCTAIRE1 restores p27 protein expression and suppresses tumor growth. Clinically, in primary tumors from patients with SCC, PCTAIRE1 is more highly expressed in malignant lesions than in adjacent normal epidermis. Conversely, expression levels of p27 are significantly lower in SCC than in normal epidermis. Conclusions: Our findings reveal a crucial function for PCTAIRE1 in regulating p27, c-Myc levels and tumor growth in cutaneous SCC cells, suggesting that PCTAIRE1 could be a novel target for skin tumor treatment.