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

Changlin Zhang,Zheng Hu,Hui Wang,Liming Wang,Wencheng Ding,Xiaoli Wang,Hui Shen,Weican Zhang,Danhui Weng,Ding Ma,Ci Ren,Lan Yu,Da Zhu,Kezhen Li,Yuan Liu,Wuguo Deng

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.

Highlights

Cervical cancer is the second most common malignant tumor after breast cancer in women worldwide [1]
The oxidative isotope-coded affinity tags (OxICAT) method screened out Voltage-dependent anion channel 1 (VDAC1), VDAC2 and VDAC3
VDAC1, VDAC2 and VDAC3, the three isoforms of VDAC, were significantly oxidized in both HPV16-positive (SiHa, S12 and CaSki) and HPV18-positive (HeLa) cervical cancer cells compared with human papillomavirus (HPV)-negative cervical cancer cells (C33A) (Figure 1A-1D)

Summary

Introduction

Cervical cancer is the second most common malignant tumor after breast cancer in women worldwide [1]. Due to widespread practice of cervical screening, most cervical cancerous and precancerous lesions can be detected and treated early [2], which can significantly reduce cervical cancer incidence and mortality, the incidence in women younger than 35 years has been increasing [3]. Infection with HPV, especially persistent infection with high-risk HPV types 16 and 18, is the major cause of cervical precancerous lesions and cancer [1, 3]. VDAC proteins, located in the outer membrane of mitochondria, constitute the mitochondrial permeability transition pore [9, 10]. Through the regulation of VDAC proteins and endometrial adenine nucleotide translocator, mitochondrial permeability transition pores open and close in a timely fashion to maintain the ion balance and membrane potential of the mitochondria [8, 11, 12]. VDAC has three isoforms: VDAC1, VDAC2 and VDAC3, all of which are important mitochondrial regulatory proteins that maintaining the normal microenvironment of the cell [9]

Methods

Results

Conclusion