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Cancer Biol Ther. 2015;16(11):1593-603. doi: 10.1080/15384047.2015.1078022. Epub 2015 Sep 21.

Chronic exposure to chewing tobacco selects for overexpression of stearoyl-CoA desaturase in normal oral keratinocytes.

Author information

1
a Institute of Bioinformatics; International Technology Park ; Bangalore , India.
2
b Amrita School of Biotechnology; Amrita University ; Kollam , India.
3
c Manipal University; Madhav Nagar ; Manipal , India.
4
d Department of Biochemistry and Molecular Biology ; Pondicherry University ; Puducherry , India.
5
e School of Biotechnology; KIIT University ; Bhubaneswar , India.
6
f Department of Otolaryngology-Head and Neck Surgery ; Johns Hopkins University School of Medicine ; Baltimore , MD USA.
7
g National Center for Cell Science (NCCS); NCCS Complex ; Pune , India.
8
h YU-IOB Center for Systems Biology and Molecular Medicine; Yenepoya University ; Mangalore , India.
9
i Milton J. Dance Head and Neck Center; Greater Baltimore Medical Center ; Baltimore , MD USA.
10
j McKusick-Nathans Institute of Genetic Medicine; Johns Hopkins University School of Medicine; Baltimore, MD USA.
11
k Department of Biological Chemistry; Johns Hopkins University School of Medicine; Baltimore, MD USA.
12
l Department of Pathology; Johns Hopkins University School of Medicine ; Baltimore , MD USA.

Abstract

Chewing tobacco is a common practice in certain socio-economic sections of southern Asia, particularly in the Indian subcontinent and has been well associated with head and neck squamous cell carcinoma. The molecular mechanisms of chewing tobacco which leads to malignancy remains unclear. In large majority of studies, short-term exposure to tobacco has been evaluated. From a biological perspective, however, long-term (chronic) exposure to tobacco mimics the pathogenesis of oral cancer more closely. We developed a cell line model to investigate the chronic effects of chewing tobacco. Chronic exposure to tobacco resulted in higher cellular proliferation and invasive ability of the normal oral keratinocytes (OKF6/TERT1). We carried out quantitative proteomic analysis of OKF6/TERT1 cells chronically treated with chewing tobacco compared to the untreated cells. We identified a total of 3,636 proteins among which expression of 408 proteins were found to be significantly altered. Among the overexpressed proteins, stearoyl-CoA desaturase (SCD) was found to be 2.6-fold overexpressed in the tobacco treated cells. Silencing/inhibition of SCD using its specific siRNA or inhibitor led to a decrease in cellular proliferation, invasion and colony forming ability of not only the tobacco treated cells but also in a panel of head and neck cancer cell lines. These findings suggest that chronic exposure to chewing tobacco induced carcinogenesis in non-malignant oral epithelial cells and SCD plays an essential role in this process. The current study provides evidence that SCD can act as a potential therapeutic target in head and neck squamous cell carcinoma, especially in patients who are users of tobacco.

KEYWORDS:

cigarette smoke; head and neck cancer; iTRAQ; mass spectrometry; smokeless tobacco; smoking

PMID:
26391970
PMCID:
PMC4846103
DOI:
10.1080/15384047.2015.1078022
[Indexed for MEDLINE]
Free PMC Article

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