TY - JOUR
T1 - Chronic Cigarette Smoke Mediated Global Changes in Lung Mucoepidermoid Cells
T2 - A Phosphoproteomic Analysis
AU - Solanki, Hitendra S.
AU - Advani, Jayshree
AU - Khan, Aafaque Ahmad
AU - Radhakrishnan, Aneesha
AU - Sahasrabuddhe, Nandini A.
AU - Pinto, Sneha M.
AU - Chang, Xiaofei
AU - Prasad, Thottethodi Subrahmanya Keshava
AU - Mathur, Premendu Prakash
AU - Sidransky, David
AU - Gowda, Harsha
AU - Chatterjee, Aditi
N1 - Funding Information:
IOB is supported by DBT Program Support on Neuro-proteomics and infrastructure for proteomic data analysis (BT/01/COE/08/05). J.A. is recipient of Senior Research Fellowship from Council of Scientific and Industrial Research (CSIR), Government of India. A.A.K. is a recipient of a Senior Research Fellowship from Indian Council of Medical Research (ICMR). S.M.P. is a recipient of INSPIRE Faculty Award from Department of Science and Technology (DST), Government of India. The authors thank Mr. Arun H. Patil for developing and providing the in-house tool for phosphoproteomic analysis. We thank Dr. S. K. Shankar and Dr. Anita Mahadevan (NIMHANS) for providing access to the microscopy imaging facility.
Funding Information:
The authors thank the Department of Biotechnology (DBT), Government of India for research support to the Institute of Bioinformatics (IOB), Bangalore. This work was supported by Department of Science and Technology (DST) grants (SERC/LS-439/2011 and SR/SO/HS/0208/ 2013) and FAMRI-funded 072017_YCSA.
Publisher Copyright:
© 2017, Mary Ann Liebert, Inc.
PY - 2017/8
Y1 - 2017/8
N2 - Proteomics analysis of chronic cigarette smoke exposure is a rapidly emerging postgenomics research field. While smoking is a major cause of lung cancer, functional studies using proteomics approaches could enrich our mechanistic understanding of the elusive lung cancer global molecular signaling and cigarette smoke relationship. We report in this study on a stable isotope labeling by amino acids in cell culture-based quantitative phosphoproteomic analysis of a human lung mucoepidermoid carcinoma cell line, H292 cells, chronically exposed to cigarette smoke. Using high resolution Orbitrap Velos mass spectrometer, we identified the hyperphosphorylation of 493 sites, which corresponds to 341 proteins and 195 hypophosphorylated sites, mapping to 142 proteins upon smoke exposure (2.0-fold change). We report differential phosphorylation of multiple kinases, including PAK6, EPHA4, LYN, mitogen-activated protein kinase, and phosphatases, including TMEM55B, PTPN14, TIGAR, among others, in response to chronic cigarette smoke exposure. Bioinformatics analysis revealed that the molecules differentially phosphorylated upon chronic exposure of cigarette smoke are associated with PI3K/AKT/mTOR and CDC42-PAK signaling pathways. These signaling networks are involved in multiple cellular processes, including cell polarity, cytoskeletal remodeling, cellular migration, protein synthesis, autophagy, and apoptosis. The present study contributes to emerging proteomics insights on cigarette smoke mediated global signaling in lung cells, which in turn may aid in development of precision medicine therapeutics and postgenomics biomarkers.
AB - Proteomics analysis of chronic cigarette smoke exposure is a rapidly emerging postgenomics research field. While smoking is a major cause of lung cancer, functional studies using proteomics approaches could enrich our mechanistic understanding of the elusive lung cancer global molecular signaling and cigarette smoke relationship. We report in this study on a stable isotope labeling by amino acids in cell culture-based quantitative phosphoproteomic analysis of a human lung mucoepidermoid carcinoma cell line, H292 cells, chronically exposed to cigarette smoke. Using high resolution Orbitrap Velos mass spectrometer, we identified the hyperphosphorylation of 493 sites, which corresponds to 341 proteins and 195 hypophosphorylated sites, mapping to 142 proteins upon smoke exposure (2.0-fold change). We report differential phosphorylation of multiple kinases, including PAK6, EPHA4, LYN, mitogen-activated protein kinase, and phosphatases, including TMEM55B, PTPN14, TIGAR, among others, in response to chronic cigarette smoke exposure. Bioinformatics analysis revealed that the molecules differentially phosphorylated upon chronic exposure of cigarette smoke are associated with PI3K/AKT/mTOR and CDC42-PAK signaling pathways. These signaling networks are involved in multiple cellular processes, including cell polarity, cytoskeletal remodeling, cellular migration, protein synthesis, autophagy, and apoptosis. The present study contributes to emerging proteomics insights on cigarette smoke mediated global signaling in lung cells, which in turn may aid in development of precision medicine therapeutics and postgenomics biomarkers.
KW - Phosphoproteomics
KW - biomarkers
KW - cigarette smoke
KW - lung cancer
KW - postgenomics biotechnology
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UR - http://www.scopus.com/inward/citedby.url?scp=85027855656&partnerID=8YFLogxK
U2 - 10.1089/omi.2017.0090
DO - 10.1089/omi.2017.0090
M3 - Article
C2 - 28816646
AN - SCOPUS:85027855656
SN - 1536-2310
VL - 21
SP - 474
EP - 487
JO - OMICS A Journal of Integrative Biology
JF - OMICS A Journal of Integrative Biology
IS - 8
ER -