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

J Dermatol Sci. 2017 May;86(2):149-157. doi: 10.1016/j.jdermsci.2017.02.281. Epub 2017 Feb 22.


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.

Keywords: Cell cycle; Cutaneous squamous cell carcinoma; Cyclin dependent kinase; p27.

MeSH terms

  • Animals
  • Apoptosis
  • Carcinogenesis
  • Carcinoma, Squamous Cell / metabolism*
  • Cell Cycle
  • Cell Division
  • Cell Proliferation
  • Cell Separation
  • Cell Survival
  • Cyclin-Dependent Kinase Inhibitor p27 / metabolism*
  • Cyclin-Dependent Kinases / metabolism*
  • Down-Regulation
  • Epidermis / metabolism
  • Flow Cytometry
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Mice
  • Neoplasm Transplantation
  • Proto-Oncogene Proteins c-myc / metabolism
  • RNA, Small Interfering / metabolism
  • Skin Neoplasms / metabolism*


  • CDKN1B protein, human
  • Proto-Oncogene Proteins c-myc
  • RNA, Small Interfering
  • Cyclin-Dependent Kinase Inhibitor p27
  • Cyclin-Dependent Kinases
  • PCTAIRE-1 protein kinase