Chronic shisha exposure alters phosphoproteome of oral keratinocytes

Shankargouda Patil, Pavithra Rajagopalan, Krishna Patel, Tejaswini Subbannayya, Niraj Babu, Sonali V. Mohan, Jayshree Advani, Gajanan Sathe, Shilpa Bhandi, Hitendra S. Solanki, David Sidransky, Aditi Chatterjee, Harsha Gowda, Marco Ferrari

Research output: Contribution to journalArticlepeer-review

Abstract

Shisha smoking has been epidemiologically linked to oral cancer. However, few studies have investigated the pathobiology of shisha-induced cellular transformation. We studied the effects of chronic shisha exposure (8 months) in an in vitro model using immortalized, non-neoplastic oral keratinocytes (OKF6/TERT1). Quantitative proteomic and phosphoproteomic analyses were performed on OKF6/TERT1 cells treated with shisha extract for a period of 8 months. Pathway analysis was carried out to identify significantly enriched biological processes in shisha-treated cells. Chronic shisha exposure resulted in increased cell scattering phenomenon in OKF6/TERT1 cells. Data analysis revealed differential phosphorylation of 164 peptides (fold change ≥1.5, p ≤ 0.0.5) corresponding to 136 proteins. Proteins associated with mTORC1 and EIF4F complexes involved in initiating protein translation were seen to be enriched upon shisha treatment. Network analysis also highlighted downregulation of proteins involved in Type I interferon signaling in shisha-treated cells. Quantitative phosphoproteomic approach elucidated global perturbations to the molecular milieu of oral keratinocytes upon shisha exposure. Further studies are needed to validate putative targets in oral cancer patients with shisha smoking history.

Original languageEnglish (US)
Pages (from-to)281-289
Number of pages9
JournalJournal of Cell Communication and Signaling
Volume13
Issue number3
DOIs
StatePublished - Sep 1 2019

Keywords

  • High-throughput
  • Hookah
  • Narghile
  • Orbitrap fusion
  • Waterpipe

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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