Proteomic and phosphoproteomic profiling of shammah induced signaling in oral keratinocytes

Abstract Shammah is a smokeless tobacco product often mixed with lime, ash, black pepper and flavorings. Exposure to shammah has been linked with dental diseases and oral squamous cell carcinoma. There is limited literature on the prevalence of shammah and its role in pathobiology of oral cancer. In...

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Autores principales: Shankargouda Patil, Mohd Younis Bhat, Jayshree Advani, Sonali V. Mohan, Niraj Babu, Keshava K. Datta, Tejaswini Subbannayya, Pavithra Rajagopalan, Firdous A. Bhat, Nezar Al-hebshi, David Sidransky, Harsha Gowda, Aditi Chatterjee
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Publicado: Nature Portfolio 2021
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spelling oai:doaj.org-article:8f0e8442e1844fe5a525d733299b371e2021-12-02T17:15:33ZProteomic and phosphoproteomic profiling of shammah induced signaling in oral keratinocytes10.1038/s41598-021-88345-x2045-2322https://doaj.org/article/8f0e8442e1844fe5a525d733299b371e2021-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-88345-xhttps://doaj.org/toc/2045-2322Abstract Shammah is a smokeless tobacco product often mixed with lime, ash, black pepper and flavorings. Exposure to shammah has been linked with dental diseases and oral squamous cell carcinoma. There is limited literature on the prevalence of shammah and its role in pathobiology of oral cancer. In this study, we developed a cellular model to understand the effect of chronic shammah exposure on oral keratinocytes. Chronic exposure to shammah resulted in increased proliferation and invasiveness of non-transformed oral keratinocytes. Quantitative proteomics of shammah treated cells compared to untreated cells led to quantification of 4712 proteins of which 402 were found to be significantly altered. In addition, phosphoproteomics analysis of shammah treated cells compared to untreated revealed hyperphosphorylation of 36 proteins and hypophosphorylation of 83 proteins (twofold, p-value ≤ 0.05). Bioinformatics analysis of significantly altered proteins showed enrichment of proteins involved in extracellular matrix interactions, necroptosis and peroxisome mediated fatty acid oxidation. Kinase-Substrate Enrichment Analysis showed significant increase in activity of kinases such as ROCK1, RAF1, PRKCE and HIPK2 in shammah treated cells. These results provide better understanding of how shammah transforms non-neoplastic cells and warrants additional studies that may assist in improved early diagnosis and treatment of shammah induced oral cancer.Shankargouda PatilMohd Younis BhatJayshree AdvaniSonali V. MohanNiraj BabuKeshava K. DattaTejaswini SubbannayyaPavithra RajagopalanFirdous A. BhatNezar Al-hebshiDavid SidranskyHarsha GowdaAditi ChatterjeeNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Shankargouda Patil
Mohd Younis Bhat
Jayshree Advani
Sonali V. Mohan
Niraj Babu
Keshava K. Datta
Tejaswini Subbannayya
Pavithra Rajagopalan
Firdous A. Bhat
Nezar Al-hebshi
David Sidransky
Harsha Gowda
Aditi Chatterjee
Proteomic and phosphoproteomic profiling of shammah induced signaling in oral keratinocytes
description Abstract Shammah is a smokeless tobacco product often mixed with lime, ash, black pepper and flavorings. Exposure to shammah has been linked with dental diseases and oral squamous cell carcinoma. There is limited literature on the prevalence of shammah and its role in pathobiology of oral cancer. In this study, we developed a cellular model to understand the effect of chronic shammah exposure on oral keratinocytes. Chronic exposure to shammah resulted in increased proliferation and invasiveness of non-transformed oral keratinocytes. Quantitative proteomics of shammah treated cells compared to untreated cells led to quantification of 4712 proteins of which 402 were found to be significantly altered. In addition, phosphoproteomics analysis of shammah treated cells compared to untreated revealed hyperphosphorylation of 36 proteins and hypophosphorylation of 83 proteins (twofold, p-value ≤ 0.05). Bioinformatics analysis of significantly altered proteins showed enrichment of proteins involved in extracellular matrix interactions, necroptosis and peroxisome mediated fatty acid oxidation. Kinase-Substrate Enrichment Analysis showed significant increase in activity of kinases such as ROCK1, RAF1, PRKCE and HIPK2 in shammah treated cells. These results provide better understanding of how shammah transforms non-neoplastic cells and warrants additional studies that may assist in improved early diagnosis and treatment of shammah induced oral cancer.
format article
author Shankargouda Patil
Mohd Younis Bhat
Jayshree Advani
Sonali V. Mohan
Niraj Babu
Keshava K. Datta
Tejaswini Subbannayya
Pavithra Rajagopalan
Firdous A. Bhat
Nezar Al-hebshi
David Sidransky
Harsha Gowda
Aditi Chatterjee
author_facet Shankargouda Patil
Mohd Younis Bhat
Jayshree Advani
Sonali V. Mohan
Niraj Babu
Keshava K. Datta
Tejaswini Subbannayya
Pavithra Rajagopalan
Firdous A. Bhat
Nezar Al-hebshi
David Sidransky
Harsha Gowda
Aditi Chatterjee
author_sort Shankargouda Patil
title Proteomic and phosphoproteomic profiling of shammah induced signaling in oral keratinocytes
title_short Proteomic and phosphoproteomic profiling of shammah induced signaling in oral keratinocytes
title_full Proteomic and phosphoproteomic profiling of shammah induced signaling in oral keratinocytes
title_fullStr Proteomic and phosphoproteomic profiling of shammah induced signaling in oral keratinocytes
title_full_unstemmed Proteomic and phosphoproteomic profiling of shammah induced signaling in oral keratinocytes
title_sort proteomic and phosphoproteomic profiling of shammah induced signaling in oral keratinocytes
publisher Nature Portfolio
publishDate 2021
url https://doaj.org/article/8f0e8442e1844fe5a525d733299b371e
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