Abstract
Cancer cells acquire unique secretome compositions that contribute to tumor development and metastasis. The aim of our study was to elucidate the biological processes involved in cervical cancer, by performing a proteomic analysis of the secretome from the following informative cervical cell lines: SiHa (HPV16+), HeLa (HPV18+), C33A (HPV−), and HCK1T (normal). Proteins were analyzed by 2D gel electrophoresis coupled to MALDI-TOF-MS. Enrichment of secreted proteins with characteristic profiles for each cell line was followed by the identification of differentially expressed proteins. Particularly, transforming growth factor-beta-induced protein ig-h3 (Beta ig-h3) and peroxiredoxin-2 (PRDX2) overexpression in the secretome of cancer cell lines was detected and confirmed by Western blot. Bioinformatics analysis identified the transcription factor NRF2 as a regulator of differentially expressed proteins in the cervical cancer secretome. NRF2 levels were measured by both Western blot and Multiple Reaction Monitoring (MRM) in the total cell extract of the four cell lines. NRF2 was upregulated in SiHa and C33A compared to HCK1T. In conclusion, the secreted proteins identified in cervical cancer cell lines indicate that aberrant NRF2-mediated oxidative stress response (OSR) is a prominent feature of cervical carcinogenesis.
Highlights
Cervical cancer belongs to a group of gynecological cancers, including vulvar and endometrial cancer that share common features, such as differentially expressed proteins, pathways, and transcription factors [1]
Proteomic studies are a valuable tool in order to explore the mechanisms involved in viral infection and protein dysfunction interplay that lead to cervical carcinogenesis [4]
We focused on the systematic evaluation of the secretome of representative cervical cancer cell lines in order to study the role of secreted proteins in cervical carcinogenesis
Summary
Cervical cancer belongs to a group of gynecological cancers, including vulvar and endometrial cancer that share common features, such as differentially expressed proteins, pathways, and transcription factors [1]. The majority of cervical cancer incidents are attributed to 13 highrisk oncogenic HPV types, represented mainly by HPV16 and HPV18. HPV infection of the cervical epithelium results in the eventual expression of E6 and E7 oncogenes, leading to sequential steps of tumor progression, corresponding to discrete histological lesions such as CIN1, CIN2, and CIN3 [3]. Infection of cervical epithelium with high-risk HPV types represents the initiating event towards cervical cancer. Proteomic studies are a valuable tool in order to explore the mechanisms involved in viral infection and protein dysfunction interplay that lead to cervical carcinogenesis [4]. Proteomic approaches have been widely utilized for the discovery of novel putative biomarkers and for understanding the mechanism of action of drugs in cervical cancer treatment [5]
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