Cervical Cancer Cell Line Secretome Highlights the Roles of Transforming Growth Factor-Beta-Induced Protein ig-h3, Peroxiredoxin-2, and NRF2 on Cervical Carcinogenesis.
Georgia KontostathiJerome ZoidakisManousos MakridakisVasiliki LygirouGeorge MermelekasTheofilos PapadopoulosKonstantinos VougasAlexios Vlamis-GardikasPeter DrakakisDimitrios LoutradisAntonia VlahouNicholas P AnagnouKalliopi I PappaPublished in: BioMed research international (2017)
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.
Keyphrases
- transforming growth factor
- oxidative stress
- transcription factor
- epithelial mesenchymal transition
- diabetic rats
- bioinformatics analysis
- high glucose
- machine learning
- south africa
- mass spectrometry
- single cell
- cell proliferation
- stem cells
- papillary thyroid
- squamous cell carcinoma
- young adults
- cell therapy
- amino acid
- anti inflammatory
- bone marrow
- dna binding
- protein protein
- small molecule
- mesenchymal stem cells
- neural network
- hyaluronic acid
- wound healing
- lymph node metastasis