TY - JOUR
T1 - Chronic exposure to chewing tobacco selects for overexpression of stearoyl-CoA desaturase in normal oral keratinocytes
AU - Nanjappa, Vishalakshi
AU - Renuse, Santosh
AU - Sathe, Gajanan J.
AU - Raja, Remya
AU - Syed, Nazia
AU - Radhakrishnan, Aneesha
AU - Subbannayya, Tejaswini
AU - Patil, Arun
AU - Marimuthu, Arivusudar
AU - Sahasrabuddhe, Nandini A.
AU - Guerrero-Preston, Rafael
AU - Somani, Babu L.
AU - Nair, Bipin
AU - Kundu, Gopal C.
AU - Prasad, T. Keshava
AU - Califano, Joseph A.
AU - Gowda, Harsha
AU - Sidransky, David
AU - Pandey, Akhilesh
AU - Chatterjee, Aditi
N1 - Publisher Copyright:
© 2015 Taylor and Francis Group, LLC.
PY - 2015/10/30
Y1 - 2015/10/30
N2 - 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.
AB - 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.
KW - cigarette smoke
KW - head and neck cancer
KW - iTRAQ
KW - mass spectrometry
KW - smokeless tobacco
KW - smoking
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U2 - 10.1080/15384047.2015.1078022
DO - 10.1080/15384047.2015.1078022
M3 - Article
C2 - 26391970
AN - SCOPUS:84948576803
SN - 1538-4047
VL - 16
SP - 1593
EP - 1603
JO - Cancer Biology and Therapy
JF - Cancer Biology and Therapy
IS - 11
ER -