Delineating Tobacco induced Cellular Transformations in Oral Cancer
Aditi Chatterjee,
Faculty Scientist,
Institute of Bioinformatics
Tobacco both in its smoked and smokeless form has been a causative agent for oral cancer. Use of both smoked and smokeless tobacco has been associated with the development of various diseases including oral cancer. However, the mechanism of action of both these forms of tobacco has not been understood at the molecular level. It is intuitive to consider that the effect of chewing and smoking tobacco would be similar, but pathobiology of oral cancer resulting from chewing tobacco may vary from cigarette smoking due to the variation in the composition of the pro-carcinogens and carcinogens. Besides, the method of intake for the two forms also varies greatly. There is incomplete knowledge of how chewing or smoking tobacco induces the early cellular changes that lead to malignancy. The first contact with tobacco products occurs in the mouth which brings about the need to study the functional consequence of tobacco chewing in oral cancer. Carcinogens present in tobacco gradually induce the process, initially expressed as dysplastic lesions, are then transformed into in situ carcinoma lesions and eventually into full-blown infiltrating and metastasizing oral cancer. Hence, it is both necessary and essential to establish a cellular model which mimics the chronic in vivo tissue exposure to chewing and smoking tobacco.
Comparing the proteins that were dysregulated between the two treatments revealed that less than handful of molecule was common between the two. This data reveals that though both chewing and smoking tobacco causes oral cancer but the molecular alterations brought about by each insult is different. Amongst the proteins which was overexpressed in both smoked and smokeless form of tobacco was Stearoyl-CoA desaturase. 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.
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