Proteomics-based identification of VDAC1 as a tumor promoter in cervical carcinoma

Oncotarget. 2016 Aug 9;7(32):52317-52328. doi: 10.18632/oncotarget.10562.

Abstract

We used oxidative isotope-coded affinity tags (OxICAT) to investigate the global redox status of proteins in human papillomavirus (HPV)-related cervical cancer cells, in order to identify a potential target for gene therapy. Voltage-dependent anion channel 1 (VDAC1) was found to be highly oxidized in HPV-positive cervical cancer cells. VDAC1 expression correlated significantly with the invasion of cervical cancer, the grade of cervical intraepithelial neoplasia (CIN) and the expression of HPV16 E7 in CIN. Knockdown of VDAC1 in cell lines increased the rate of apoptosis, while overexpression of the VDAC1 (respectively) partly reversed the effect. Thus, VDAC1 may promote the malignant progression of HPV-related disease, and treatments designed to suppress VDAC1 could prevent the progression of HPV-induced cervical disease.

Keywords: HPV16 E7; VDAC1; cervical cancer; proteomics; immunohistochemistry (IHC).

MeSH terms

  • Carcinogens / metabolism
  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Squamous Cell / pathology*
  • Carcinoma, Squamous Cell / virology
  • Female
  • Humans
  • Oxidation-Reduction
  • Papillomavirus E7 Proteins / metabolism
  • Papillomavirus Infections / complications
  • Proteomics / methods
  • Uterine Cervical Neoplasms / metabolism
  • Uterine Cervical Neoplasms / pathology*
  • Uterine Cervical Neoplasms / virology
  • Voltage-Dependent Anion Channel 1 / metabolism*

Substances

  • Carcinogens
  • Papillomavirus E7 Proteins
  • VDAC1 protein, human
  • oncogene protein E7, Human papillomavirus type 16
  • Voltage-Dependent Anion Channel 1