Dataset Information

Molecular alterations elicited by chronic exposure to cigarette smoke in oral keratinocytes

ABSTRACT: Smoking is the leading cause of preventable death worldwide. It increases the risk for various diseases including respiratory diseases, vascular diseases and different cancers including lung, oral and bladder cancer. Despite being the leading cause of oral cancer, the molecular mechanisms resulting in malignancy upon cigarette smoke exposure are yet to be fully elucidated. It is crucial to note that disease development is observed upon chronic exposure to cigarette smoke, as opposed to a short-term exposure. Hence, we sought to investigate the effect of chronic smoke exposure on normal oral keratinocytes (OKF6/TERT1). We employed tandem mass tag-based quantitative proteomic and phosphoproteomic approaches to investigate the proteomic and signaling changes in OKF6/TERT1 cells chronically exposed to cigarette smoke compared to untreated cells. LC/MS2 analysis resulted in the quantification of 5,067 proteins among which expression of 360 proteins were found to be dysregulated in at least one replicate. Phosphoproteomic analysis revealed quantification of 3,647 phosphopeptides corresponding to 1,801 proteins. Majority of the dysregulated proteins were seen to be involved in cellular processes such as cell growth, cellular communication and energy metabolism. This study will aid in elucidating the effects of smoking in oral cancer and in the identification of potential candidates molecules which could serve as early detection biomarkers or therapeutic targets.

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Oral Epithelium

SUBMITTER: Aditi Chatterjee

LAB HEAD: Aditi Chatterjee

PROVIDER: PXD007637 | Pride | 2018-03-05

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	OKF6_CSC_Total_011916.msf	Msf
	OKF6_CSC_Total_011916.pdResult	Other
	OKF6_CSC_phospho10.raw	Raw
	OKF6_CSC_phospho11.raw	Raw
	OKF6_CSC_phospho12.raw	Raw

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Publications

Role of protein kinase N2 (PKN2) in cigarette smoke-mediated oncogenic transformation of oral cells.

Rajagopalan Pavithra P Nanjappa Vishalakshi V Patel Krishna K Jain Ankit P AP Mangalaparthi Kiran K KK Patil Arun H AH Nair Bipin B Mathur Premendu P PP Keshava Prasad T S TS Califano Joseph A JA Sidransky David D Gowda Harsha H Chatterjee Aditi A

Journal of cell communication and signaling 20180226 4

Smoking is the leading cause of preventable death worldwide. Though cigarette smoke is an established cause of head and neck cancer (including oral cancer), molecular alterations associated with chronic cigarette smoke exposure are poorly studied. To understand the signaling alterations induced by chronic exposure to cigarette smoke, we developed a cell line model by exposing normal oral keratinocytes to cigarette smoke for a period of 12 months. Chronic exposure to cigarette smoke resulted in i ...[more]

PMID: 29480433

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Project description:Esophageal squamous cell carcinoma (ESCC) is one of the most common cancers with high mortality rate. Smoking is one of the established risk factors of ESCC. However, there is limited data on molecular alterations associated with cigarette smoke exposure in esophageal cells. Understanding the effects of cigarette smoke on esophageal squamous epithelial cells at a molecular level would lead to a better understanding of the pathobiology of ESCC which has implications for identification of early biomarkers and therapeutic targets. To investigate the effect of cigarette smoke exposure, we developed a cell line model where Het1A cells (non-neoplastic human esophageal epithelial cells) were chronically treated with cigarette smoke condensate (CSC) for 2 months, 4 months, 6 months and 8 months. We carried out comparative proteomic, phosphoproteomic and whole exome sequencing analyses on CSC treated and untreated cells. Increased cell proliferation and invasion of Het1A cells was observed after chronic exposure to cigarette smoke. Using quantitative proteomic and phosphoproteomic analyses, we identified 56 proteins and 296 phosphoproteins that showed differential expression. Bioinformatics analysis of differentially expressed proteins and phosphoproteins showed enrichment of molecules involved in DNA damage response pathway. Whole exome sequencing (WES) of CSC treated and untreated cells also revealed mutations and copy number alterations in genes associated with DNA damage response. By correlating WES, proteomic and phosphoproteomic results, we observed potential loss of function in HMGN2 and MED1 that were reported as potential tumor suppressors and are known to play important role in DNA damage response. We also observed decreased expression of HMGN2 in tissue section of ESCC. Overexpression of HMGN2 and MED1 lead to decreased proliferative and invasive ability of CSC treated cells. These findings suggest that cigarette smoke affects genes and proteins associated with DNA damage response pathways which might play a vital role in development of ESCC.