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

Pavithra Rajagopalan, Krishna Patel, Ankit P. Jain, Vishalakshi Nanjappa, Keshava K. Datta, Tejaswini Subbannayya, Kiran K. Mangalaparthi, Anjali Kumari, Malini Manoharan, Karunakaran Coral, Sakthivel Murugan, Bipin Nair, T. S.Keshava Prasad, Premendu P. Mathur, Ravi Gupta, Rohit Gupta, Arati Khanna-Gupta, Joseph Califano, David Sidransky, Harsha GowdaAditi Chatterjee

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)773-785
Number of pages13
JournalCancer Biology and Therapy
Volume19
Issue number9
DOIs
StatePublished - Sep 2 2018

Keywords

  • Orbitrap Fusion
  • carcinogenesis
  • chronic exposure
  • high-throughput
  • smoking

ASJC Scopus subject areas

  • Molecular Medicine
  • Oncology
  • Pharmacology
  • Cancer Research

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