FBXW7 Mutations Promote Cell Proliferation, Migration, and Invasion in Cervical Cancer

Genet Test Mol Biomarkers. 2019 Jun;23(6):409-417. doi: 10.1089/gtmb.2018.0278.

Abstract

Aim: Cervical cancer is the most common gynecological cancer. Recent studies have revealed that the F-box and WD repeat domain containing 7 (FBXW7) gene, which encodes a subunit of Skp1-Cul1-F-box protein (SCF) ubiquitin ligase, is frequently mutated in cervical squamous cell carcinomas. In this study, we investigated whether Chinese cervical cancer cells also harbor these mutations. Methods: Using PCR and sequencing assays, a total of 190 specimens from Han Chinese patients with cervical cancer were analyzed for FBXW7 mutations. Results: Two FBXW7 mutations (p.R479P and p.L443H), were identified from a study of 145 (1.4%) cervical squamous cell carcinomas. The p.L443H somatic mutation has not been previously reported. Functional assays showed that both of these FBXW7 mutations could promote cell proliferation, migration, and invasion. Conclusion: A low frequency (1.4%) of cervical squamous cell carcinomas were identified with FBXW7 mutations. We did, however, identify a novel FBXW7 mutation. Our results also demonstrated that the identified FBXW7 mutations could promote cell proliferation, migration, and invasion in cervical cancer cells.

Keywords: mutations; cell proliferation; cervical cancer; invasion; migration.

MeSH terms

  • Adult
  • Aged
  • Asian People / genetics
  • Carcinoma, Squamous Cell / genetics
  • Cell Cycle Proteins
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • China
  • F-Box Proteins
  • F-Box-WD Repeat-Containing Protein 7 / genetics*
  • F-Box-WD Repeat-Containing Protein 7 / physiology
  • Female
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • Middle Aged
  • Mutation / genetics
  • Neoplasm Invasiveness / genetics
  • Uterine Cervical Neoplasms / genetics*

Substances

  • Cell Cycle Proteins
  • F-Box Proteins
  • F-Box-WD Repeat-Containing Protein 7
  • FBXW7 protein, human