Dataset Information

P21-Activated kinase 6 (PAK6) is associated with enhanced proliferation in lung cells exposed chronically to cigarette smoke

ABSTRACT: Epidemiological data clearly establishes cigarette smoking as one of the major cause for lung cancer worldwide. There is no standard screening method for lung cancer even in high-risk populations and the overall five-year survival has not changed significantly in the last decade. First-line treatment for lung cancer includes surgical resection, chemotherapy, and radiation. Recently with the advancement of systems biology, targeted therapy has become one of the most preferred modes of treatment for cancer. Though certain targeted therapies such as anti-EGFR are in clinical practice, they have shown limited success in the smokers suffering from lung cancer. This demands the discovery of alternative drug targets through systematic investigation of altered signaling mechanisms. To study dysregulated signaling pathways due to chronic cigarette smzoke exposure, we carried out SILAC-based phosphoproteome analysis of lung cell line H358 chronically exposed to cigarette smoke. We identified 1,812 phosphosites, of which 278 were hyperphosphorylated (≥ 3-fold) in the H358 cells exposed to cigarette smoke. We identified several known and some novel kinases and key signaling molecules that were hyperphosphorylated in response to chronic exposure to cigarette smoke

INSTRUMENT(S): LTQ Orbitrap Velos

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Epithelial Cell, Cell Culture

DISEASE(S): Non-small Cell Lung Carcinoma

SUBMITTER: Akhilesh Pandey

LAB HEAD: Akhilesh Pandey

PROVIDER: PXD003108 | Pride | 2016-12-14

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	H358_SILAC_CSC_pSTY_01.raw	Raw
	H358_SILAC_CSC_pSTY_02.raw	Raw
	H358_SILAC_CSC_pSTY_03.raw	Raw
	H358_SILAC_CSC_pSTY_04.raw	Raw
	H358_SILAC_CSC_pSTY_05.raw	Raw

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Publications

Chronic exposure to cigarette smoke leads to activation of p21 (RAC1)-activated kinase 6 (PAK6) in non-small cell lung cancer cells.

Raja Remya R Sahasrabuddhe Nandini A NA Radhakrishnan Aneesha A Syed Nazia N Solanki Hitendra S HS Puttamallesh Vinuth N VN Balaji Sai A SA Nanjappa Vishalakshi V Datta Keshava K KK Babu Niraj N Renuse Santosh S Patil Arun H AH Izumchenko Evgeny E Prasad T S Keshava TS Chang Xiaofei X Rangarajan Annapoorni A Sidransky David D Pandey Akhilesh A Gowda Harsha H Chatterjee Aditi A

Oncotarget 20160901 38

Epidemiological data clearly establishes cigarette smoking as one of the major cause for lung cancer worldwide. Recently, targeted therapy has become one of the most preferred modes of treatment for cancer. Though certain targeted therapies such as anti-EGFR are in clinical practice, they have shown limited success in lung cancer patients who are smokers. This demands discovery of alternative drug targets through systematic investigation of cigarette smoke-induced signaling mechanisms. To study ...[more]

PMID: 27542207

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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.