title: Chronic exposure to chewing tobacco selects for overexpression of stearoyl-CoA desaturase in normal oral keratinocytes.
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.
authors.affiliation: a Institute of Bioinformatics; International Technology Park ; Bangalore , India.|b Amrita School of Biotechnology; Amrita University ; Kollam , India.
authors.forename: Vishalakshi
authors.initials: V
authors.lastname: Nanjappa
authors.affiliation: a Institute of Bioinformatics; International Technology Park ; Bangalore , India.|b Amrita School of Biotechnology; Amrita University ; Kollam , India.
authors.forename: Santosh
authors.initials: S
authors.lastname: Renuse
authors.affiliation: a Institute of Bioinformatics; International Technology Park ; Bangalore , India.|c Manipal University; Madhav Nagar ; Manipal , India.
authors.forename: Gajanan J
authors.initials: GJ
authors.lastname: Sathe
authors.affiliation: a Institute of Bioinformatics; International Technology Park ; Bangalore , India.
authors.forename: Remya
authors.initials: R
authors.lastname: Raja
authors.affiliation: a Institute of Bioinformatics; International Technology Park ; Bangalore , India.|d Department of Biochemistry and Molecular Biology ; Pondicherry University ; Puducherry , India.
authors.forename: Nazia
authors.initials: N
authors.lastname: Syed
authors.affiliation: a Institute of Bioinformatics; International Technology Park ; Bangalore , India.|d Department of Biochemistry and Molecular Biology ; Pondicherry University ; Puducherry , India.
authors.forename: Aneesha
authors.initials: A
authors.lastname: Radhakrishnan
authors.affiliation: a Institute of Bioinformatics; International Technology Park ; Bangalore , India.|b Amrita School of Biotechnology; Amrita University ; Kollam , India.
authors.forename: Tejaswini
authors.initials: T
authors.lastname: Subbannayya
authors.affiliation: a Institute of Bioinformatics; International Technology Park ; Bangalore , India.|e School of Biotechnology; KIIT University ; Bhubaneswar , India.
authors.forename: Arun
authors.initials: A
authors.lastname: Patil
authors.affiliation: a Institute of Bioinformatics; International Technology Park ; Bangalore , India.
authors.forename: Arivusudar
authors.initials: A
authors.lastname: Marimuthu
authors.affiliation: a Institute of Bioinformatics; International Technology Park ; Bangalore , India.
authors.forename: Nandini A
authors.initials: NA
authors.lastname: Sahasrabuddhe
authors.affiliation: f Department of Otolaryngology-Head and Neck Surgery ; Johns Hopkins University School of Medicine ; Baltimore , MD USA.
authors.forename: Rafael
authors.initials: R
authors.lastname: Guerrero-Preston
authors.affiliation: a Institute of Bioinformatics; International Technology Park ; Bangalore , India.
authors.forename: Babu L
authors.initials: BL
authors.lastname: Somani
authors.affiliation: b Amrita School of Biotechnology; Amrita University ; Kollam , India.
authors.forename: Bipin
authors.initials: B
authors.lastname: Nair
authors.affiliation: g National Center for Cell Science (NCCS); NCCS Complex ; Pune , India.
authors.forename: Gopal C
authors.initials: GC
authors.lastname: Kundu
authors.affiliation: a Institute of Bioinformatics; International Technology Park ; Bangalore , India.|b Amrita School of Biotechnology; Amrita University ; Kollam , India.|h YU-IOB Center for Systems Biology and Molecular Medicine; Yenepoya University ; Mangalore , India.
authors.forename: T Keshava
authors.initials: TK
authors.lastname: Prasad
authors.affiliation: f Department of Otolaryngology-Head and Neck Surgery ; Johns Hopkins University School of Medicine ; Baltimore , MD USA.|i Milton J. Dance Head and Neck Center; Greater Baltimore Medical Center ; Baltimore , MD USA.
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Califano
authors.affiliation: a Institute of Bioinformatics; International Technology Park ; Bangalore , India.|h YU-IOB Center for Systems Biology and Molecular Medicine; Yenepoya University ; Mangalore , India.
authors.forename: Harsha
authors.initials: H
authors.lastname: Gowda
authors.affiliation: f Department of Otolaryngology-Head and Neck Surgery ; Johns Hopkins University School of Medicine ; Baltimore , MD USA.
authors.forename: David
authors.initials: D
authors.lastname: Sidransky
authors.affiliation: j McKusick-Nathans Institute of Genetic Medicine; Johns Hopkins University School of Medicine; Baltimore, MD USA.|k Department of Biological Chemistry; Johns Hopkins University School of Medicine; Baltimore, MD USA.|l Department of Pathology; Johns Hopkins University School of Medicine ; Baltimore , MD USA.
authors.forename: Akhilesh
authors.initials: A
authors.lastname: Pandey
authors.affiliation: a Institute of Bioinformatics; International Technology Park ; Bangalore , India.|h YU-IOB Center for Systems Biology and Molecular Medicine; Yenepoya University ; Mangalore , India.
authors.forename: Aditi
authors.initials: A
authors.lastname: Chatterjee
mesh_terms: D063646:Carcinogenesis / Q000378:metabolism; D002460:Cell Line; D002465:Cell Movement; D049109:Cell Proliferation; D004790:Enzyme Induction; D006801:Humans; D015603:Keratinocytes / Q000201:enzymology*; D009061:Mouth Mucosa / Q000473:pathology; D009062:Mouth Neoplasms / Q000209:etiology / Q000473:pathology; D020543:Proteome / Q000378:metabolism; D013230:Stearoyl-CoA Desaturase / Q000235:genetics / Q000378:metabolism*; D064424:Tobacco Use / Q000009:adverse effects / Q000378:metabolism* / Q000473:pathology; D014026:Nicotiana
chemical_list: D020543:Proteome; D013230:Stearoyl-CoA Desaturase
keywords: cigarette smoke; head and neck cancer; iTRAQ; mass spectrometry; smokeless tobacco; smoking