Dataset Information

A multi-omic analysis to characterize cigarette smoke induced molecular alterations in esophageal cells: phosphoproteomics

ABSTRACT: 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.

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Epithelium Of Esophagus

SUBMITTER: Harsha Gowda

LAB HEAD: Harsha Gowda

PROVIDER: PXD007814 | Pride | 2021-09-07

REPOSITORIES: Pride

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Publications

Multi-Omics Analysis to Characterize Cigarette Smoke Induced Molecular Alterations in Esophageal Cells.

Khan Aafaque Ahmad AA Patel Krishna K Patil Shankargouda S Babu Niraj N Mangalaparthi Kiran K KK Solanki Hitendra Singh HS Nanjappa Vishalakshi V Kumari Anjali A Manoharan Malini M Karunakaran Coral C Murugan Saktivel S Nair Bipin B Kumar Rekha V RV Biswas Manjusha M Sidransky David D Gupta Ravi R Gupta Rohit R Khanna-Gupta Arati A Kumar Prashant P Chatterjee Aditi A Gowda Harsha H

Frontiers in oncology 20201105

Though smoking remains one of the established risk factors of esophageal squamous cell carcinoma, there is limited data on molecular alterations associated with cigarette smoke exposure in esophageal cells. To investigate molecular alterations associated with chronic exposure to cigarette smoke, non-neoplastic human esophageal epithelial cells were treated with cigarette smoke condensate (CSC) for up to 8 months. Chronic treatment with CSC increased cell proliferation and invasive ability of non ...[more]

PMID: 33251127

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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.

			Action	DRS
	Het1A_Phospho_R1_1.msf	Msf
	Het1A_Phospho_R1_1.raw	Raw
	Het1A_Phospho_R1_10.msf	Msf
	Het1A_Phospho_R1_10.raw	Raw
	Het1A_Phospho_R1_11.msf	Msf