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ABSTRACT: Metagenome of Indian domestic smokeless tobacco products

PROVIDER: PRJNA1026832 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR26715255_1.fastq.gz	Fastqsanger.gz
	SRR26715255_2.fastq.gz	Fastqsanger.gz
	SRR26715256_1.fastq.gz	Fastqsanger.gz
	SRR26715256_2.fastq.gz	Fastqsanger.gz
	SRR26715257_1.fastq.gz	Fastqsanger.gz

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Project description:Tobacco in its smoke and smokeless form are major risk factors for ESCC (esophageal squamous cell carcinoma). However, molecular alterations associated with smokeless tobacco exposure are poorly understood. In the Indian subcontinent, tobacco is predominantly consumed in chewing form. An understanding of molecular alterations associated with chewing tobacco exposure is vital for identifying molecular markers and potential targets. We developed an in-vitro cellular model by exposing non-transformed esophageal epithelial cells to chewing tobacco over eight month period. Chronic exposure to chewing tobacco led to increase in cell proliferation, invasive ability and anchorage independent growth indicating cell transformation. Molecular alterations associated with chewing tobacco exposure were characterized by carrying out exome sequencing and quantitative proteomic profiling of parental cells and chewing tobacco exposed cells. Quantitative proteomic analysis revealed that established cancer stem cell markers are elevated in tobacco treated cells. Decreased expression of enzymes associated with the glycolytic pathway and increased expression of a large number of mitochondrially localized proteins involved in the electron transport chain as well as enzymes of TCA cycle were also identified. Electron micrographs revealed increase in number and size of mitochondria. Based on these observations, we hypothesise that chronic treatment of esophageal epithelial cells with tobacco leads to a cancer stem cell-like phenotype. These cells also show characteristic OXPHOS phenotype which can be potentially targeted as a therapeutic strategy.

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