Chronic Cigarette Smoke Mediated Global Changes in Lung Mucoepidermoid Cells: A Phosphoproteomic Analysis

Hitendra S. Solanki, Jayshree Advani, Aafaque Ahmad Khan, Aneesha Radhakrishnan, Nandini A. Sahasrabuddhe, Sneha M. Pinto, Xiaofei Chang, Thottethodi Subrahmanya Keshava Prasad, Premendu Prakash Mathur, David Sidransky, Harsha Gowda, Aditi Chatterjee

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)474-487
Number of pages14
JournalOMICS A Journal of Integrative Biology
Volume21
Issue number8
DOIs
StatePublished - Aug 2017

Keywords

  • Phosphoproteomics
  • biomarkers
  • cigarette smoke
  • lung cancer
  • postgenomics biotechnology

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Genetics

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