PCTAIRE1/CDK16/PCTK1 is overexpressed in cutaneous squamous cell carcinoma and regulates p27 stability and cell cycle

Teruki Yanagi, Hiroo Hata, Eri Mizuno, Shinya Kitamura, Keisuke Imafuku, Shinichi Nakazato, Lei Wang, Hiroshi Nishihara, Shinya Tanaka, Hiroshi Shimizu

Research output: Contribution to journalArticle

8 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)149-157
Number of pages9
JournalJournal of Dermatological Science
Volume86
Issue number2
DOIs
Publication statusPublished - 2017 May 1
Externally publishedYes

Fingerprint

Tumors
Squamous Cell Carcinoma
Cell Cycle
Cells
Skin
Neoplasms
Cyclin-Dependent Kinases
Epidermis
Carcinogenesis
Colony-Forming Units Assay
Gene Knockdown Techniques
Annexin A5
Cell proliferation
Heterografts
Spermatogenesis
Growth
Epithelial Cells
Assays
Proteins
Genes

Keywords

  • Cell cycle
  • Cutaneous squamous cell carcinoma
  • Cyclin dependent kinase
  • p27

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology

Cite this

PCTAIRE1/CDK16/PCTK1 is overexpressed in cutaneous squamous cell carcinoma and regulates p27 stability and cell cycle. / Yanagi, Teruki; Hata, Hiroo; Mizuno, Eri; Kitamura, Shinya; Imafuku, Keisuke; Nakazato, Shinichi; Wang, Lei; Nishihara, Hiroshi; Tanaka, Shinya; Shimizu, Hiroshi.

In: Journal of Dermatological Science, Vol. 86, No. 2, 01.05.2017, p. 149-157.

Research output: Contribution to journalArticle

Yanagi, T, Hata, H, Mizuno, E, Kitamura, S, Imafuku, K, Nakazato, S, Wang, L, Nishihara, H, Tanaka, S & Shimizu, H 2017, 'PCTAIRE1/CDK16/PCTK1 is overexpressed in cutaneous squamous cell carcinoma and regulates p27 stability and cell cycle', Journal of Dermatological Science, vol. 86, no. 2, pp. 149-157. https://doi.org/10.1016/j.jdermsci.2017.02.281
Yanagi, Teruki ; Hata, Hiroo ; Mizuno, Eri ; Kitamura, Shinya ; Imafuku, Keisuke ; Nakazato, Shinichi ; Wang, Lei ; Nishihara, Hiroshi ; Tanaka, Shinya ; Shimizu, Hiroshi. / PCTAIRE1/CDK16/PCTK1 is overexpressed in cutaneous squamous cell carcinoma and regulates p27 stability and cell cycle. In: Journal of Dermatological Science. 2017 ; Vol. 86, No. 2. pp. 149-157.
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AU - Yanagi, Teruki

AU - Hata, Hiroo

AU - Mizuno, Eri

AU - Kitamura, Shinya

AU - Imafuku, Keisuke

AU - Nakazato, Shinichi

AU - Wang, Lei

AU - Nishihara, Hiroshi

AU - Tanaka, Shinya

AU - Shimizu, Hiroshi

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N2 - 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.

AB - 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.

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