PCTAIRE1/CDK16/PCTK1 is overexpressed in cutaneous squamous cell carcinoma and regulates p27 stability and cell cycle
PCTAIRE1/CDK16/PCTK1 is overexpressed in cutaneous squamous cell carcinoma and regulates p27 stability and cell cycle
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DOI：
10.1016/j.jdermsci.2017.02.281
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发表时间：
2017-05-01
影响因子：
4.6
通讯作者：
Shimizu, Hiroshi
中科院分区：
文献类型：
--
作者：
Yanagi, Teruki;Hata, Hiroo;Shimizu, Hiroshi
背景：PCTAIRE1(又称细胞周期蛋白依赖性激酶16，CDK16和PCTK1)是一种CDK家族蛋白，参与精子发生。目的：本研究探讨了PCTAIRE1在皮肤鳞状细胞癌发生中的作用。方法和结果：在皮肤/口腔鳞状细胞癌A431、DJM-1、HSC-3细胞中，PCTAIRE1基因敲除可抑制细胞增殖。FACS膜联蛋白V-PI染色和DNA含量分析显示，PCTAIRE1基因被敲除后导致G2/M期停滞，继而发生细胞凋亡。PCTAIRE1基因缺失导致抑癌基因p27积聚，c-Myc表达下调。在A431细胞的移植瘤中，PCTAIRE1的条件性敲除恢复了p27蛋白的表达，抑制了肿瘤的生长。临床上，在鳞癌患者的原发肿瘤中，PCTAIRE1在恶性病变中的表达高于邻近正常皮肤。结论：PCTAIRE1在皮肤SCC细胞中具有调节p27、c-Myc水平和肿瘤生长的重要作用，提示PCTAIRE1可能成为皮肤肿瘤治疗的新靶点。(C)2017年日本皮肤病研究学会。爱思唯尔爱尔兰有限公司出版。版权所有。
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. (C) 2017 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.