CDK1 Promotes Epithelial-Mesenchymal Transition and Migration of Head and Neck Squamous Carcinoma Cells by Repressing ∆Np63α-Mediated Transcriptional Regulation

Int J Mol Sci. 2022 Jul 2;23(13):7385. doi: 10.3390/ijms23137385.

Abstract

∆Np63α is a key transcription factor overexpressed in types of squamous cell carcinomas (SCCs), which represses epithelial-mesenchymal transition (EMT) and cell migration. In this study, we found that CDK1 phosphorylates ∆Np63α at the T123 site, impairing its affinity to the target promoters of its downstream genes and its regulation of them in turn. Database analysis revealed that CDK1 is overexpressed in head and neck squamous cell carcinomas (HNSCCs), especially the metastatic HNSCCs, and is negatively correlated with overall survival. We further found that CDK1 promotes the EMT and migration of HNSCC cells by inhibiting ∆Np63α. Altogether, our study identified CDK1 as a novel regulator of ΔNp63α, which can modulate EMT and cell migration in HNSCCs. Our findings will help to elucidate the migration mechanism of HNSCC cells.

Keywords: CDK1; cell migration; epithelial–mesenchymal transition (EMT); head and neck squamous cell carcinoma (HNSCC); kinase; phosphorylation; transcriptional regulation; ∆Np63α.

MeSH terms

  • CDC2 Protein Kinase* / genetics
  • CDC2 Protein Kinase* / metabolism
  • Cell Line, Tumor
  • Cell Movement / physiology
  • Epithelial-Mesenchymal Transition
  • Head and Neck Neoplasms* / genetics
  • Head and Neck Neoplasms* / metabolism
  • Head and Neck Neoplasms* / pathology
  • Humans
  • Squamous Cell Carcinoma of Head and Neck* / genetics
  • Squamous Cell Carcinoma of Head and Neck* / metabolism
  • Squamous Cell Carcinoma of Head and Neck* / pathology
  • Transcription Factors* / genetics
  • Transcription Factors* / metabolism
  • Transcription, Genetic
  • Tumor Suppressor Proteins* / genetics
  • Tumor Suppressor Proteins* / metabolism

Substances

  • TP63 protein, human
  • Transcription Factors
  • Tumor Suppressor Proteins
  • CDC2 Protein Kinase
  • CDK1 protein, human