Molecular alterations associated with chronic exposure to cigarette smoke and chewing tobacco in normal oral keratinocytes

Tobacco usage is a known risk factor associated with development of oral cancer. It is mainly consumed in two different forms (smoking and chewing) that vary in their composition and methods of intake. Despite being the leading cause of oral cancer, molecular alterations induced by tobacco are poorl...

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Published in:Cancer biology & therapy 2018-09, Vol.19 (9), p.773-785
Main Authors: Rajagopalan, Pavithra, Patel, Krishna, Jain, Ankit P., Nanjappa, Vishalakshi, Datta, Keshava K., Subbannayya, Tejaswini, Mangalaparthi, Kiran K., Kumari, Anjali, Manoharan, Malini, Coral, Karunakaran, Murugan, Sakthivel, Nair, Bipin, Prasad, T. S. Keshava, Mathur, Premendu P., Gupta, Ravi, Gupta, Rohit, Khanna-Gupta, Arati, Califano, Joseph, Sidransky, David, Gowda, Harsha, Chatterjee, Aditi
Format: Article
Language:English
Subjects:
Biomarkers
carcinogenesis
Cell Transformation, Neoplastic
chronic exposure
Environmental Exposure
Gene Expression Profiling
high-throughput
Humans
Keratinocytes - metabolism
Mouth Mucosa - cytology
Orbitrap Fusion
Phenotype
Proteome
Proteomics - methods
Research Paper
smoking
Smoking - adverse effects
Tobacco Use - adverse effects
Transcriptome
Whole Exome Sequencing
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Summary:Tobacco usage is a known risk factor associated with development of oral cancer. It is mainly consumed in two different forms (smoking and chewing) that vary in their composition and methods of intake. Despite being the leading cause of oral cancer, molecular alterations induced by tobacco are poorly understood. We therefore sought to investigate the adverse effects of cigarette smoke/chewing tobacco exposure in oral keratinocytes (OKF6/TERT1). OKF6/TERT1 cells acquired oncogenic phenotype after treating with cigarette smoke/chewing tobacco for a period of 8 months. We employed whole exome sequencing (WES) and quantitative proteomics to investigate the molecular alterations in oral keratinocytes chronically exposed to smoke/ chewing tobacco. Exome sequencing revealed distinct mutational spectrum and copy number alterations in smoke/ chewing tobacco treated cells. We also observed differences in proteomic alterations. Proteins downstream of MAPK1 and EGFR were dysregulated in smoke and chewing tobacco exposed cells, respectively. This study can serve as a reference for fundamental damages on oral cells as a consequence of exposure to different forms of tobacco.
ISSN:1538-4047
1555-8576
DOI:10.1080/15384047.2018.1470724