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NGAL is Downregulated in Oral Squamous Cell Carcinoma and Leads to Increased Survival, Proliferation, Migration and Chemoresistance

Oral cancer is a major public health burden worldwide. The lack of biomarkers for early diagnosis has increased the difficulty in managing this disease. Recent studies have reported that neutrophil gelatinase-associated lipocalin (NGAL), a secreted glycoprotein, is upregulated in various tumors. In...

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Autores principales: Monisha, Javadi, Roy, Nand Kishor, Padmavathi, Ganesan, Banik, Kishore, Bordoloi, Devivasha, Khwairakpam, Amrita Devi, Arfuso, Frank, Chinnathambi, Arunachalam, Alahmadi, Tahani Awad, Alharbi, Sulaiman Ali, Sethi, Gautam, Kumar, Alan Prem, Kunnumakkara, Ajaikumar B.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6071146/
https://www.ncbi.nlm.nih.gov/pubmed/29996471
http://dx.doi.org/10.3390/cancers10070228
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author Monisha, Javadi
Roy, Nand Kishor
Padmavathi, Ganesan
Banik, Kishore
Bordoloi, Devivasha
Khwairakpam, Amrita Devi
Arfuso, Frank
Chinnathambi, Arunachalam
Alahmadi, Tahani Awad
Alharbi, Sulaiman Ali
Sethi, Gautam
Kumar, Alan Prem
Kunnumakkara, Ajaikumar B.
author_facet Monisha, Javadi
Roy, Nand Kishor
Padmavathi, Ganesan
Banik, Kishore
Bordoloi, Devivasha
Khwairakpam, Amrita Devi
Arfuso, Frank
Chinnathambi, Arunachalam
Alahmadi, Tahani Awad
Alharbi, Sulaiman Ali
Sethi, Gautam
Kumar, Alan Prem
Kunnumakkara, Ajaikumar B.
author_sort Monisha, Javadi
collection PubMed
description Oral cancer is a major public health burden worldwide. The lack of biomarkers for early diagnosis has increased the difficulty in managing this disease. Recent studies have reported that neutrophil gelatinase-associated lipocalin (NGAL), a secreted glycoprotein, is upregulated in various tumors. In our study, we found that NGAL was significantly downregulated in primary malignant and metastatic tissues of oral cancer in comparison to normal tissues. The downregulation of NGAL was strongly correlated with both degree of differentiation and stage (I–IV); it can also serve as a prognostic biomarker for oral cancer. Additionally, tobacco carcinogens were found to be involved in the downregulation of NGAL. Mechanistic studies revealed that knockdown of NGAL increased oral cancer cell proliferation, survival, and migration; it also induced resistance against cisplatin. Silencing of NGAL activated mammalian target of rapamycin (mTOR)signaling and reduced autophagy by the liver kinase B1 (LKB1)-activated protein kinase (AMPK)-p53-Redd1 signaling axis. Moreover, cyclin-D1, Bcl-2, and matrix metalloproteinase-9 (MMP-9) were upregulated, and caspase-9 was downregulated, suggesting that silencing of NGAL increases oral cancer cell proliferation, survival, and migration. Thus, from our study, it is evident that downregulation of NGAL activates the mTOR pathway and helps in the progression of oral cancer.
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spelling pubmed-60711462018-08-09 NGAL is Downregulated in Oral Squamous Cell Carcinoma and Leads to Increased Survival, Proliferation, Migration and Chemoresistance Monisha, Javadi Roy, Nand Kishor Padmavathi, Ganesan Banik, Kishore Bordoloi, Devivasha Khwairakpam, Amrita Devi Arfuso, Frank Chinnathambi, Arunachalam Alahmadi, Tahani Awad Alharbi, Sulaiman Ali Sethi, Gautam Kumar, Alan Prem Kunnumakkara, Ajaikumar B. Cancers (Basel) Article Oral cancer is a major public health burden worldwide. The lack of biomarkers for early diagnosis has increased the difficulty in managing this disease. Recent studies have reported that neutrophil gelatinase-associated lipocalin (NGAL), a secreted glycoprotein, is upregulated in various tumors. In our study, we found that NGAL was significantly downregulated in primary malignant and metastatic tissues of oral cancer in comparison to normal tissues. The downregulation of NGAL was strongly correlated with both degree of differentiation and stage (I–IV); it can also serve as a prognostic biomarker for oral cancer. Additionally, tobacco carcinogens were found to be involved in the downregulation of NGAL. Mechanistic studies revealed that knockdown of NGAL increased oral cancer cell proliferation, survival, and migration; it also induced resistance against cisplatin. Silencing of NGAL activated mammalian target of rapamycin (mTOR)signaling and reduced autophagy by the liver kinase B1 (LKB1)-activated protein kinase (AMPK)-p53-Redd1 signaling axis. Moreover, cyclin-D1, Bcl-2, and matrix metalloproteinase-9 (MMP-9) were upregulated, and caspase-9 was downregulated, suggesting that silencing of NGAL increases oral cancer cell proliferation, survival, and migration. Thus, from our study, it is evident that downregulation of NGAL activates the mTOR pathway and helps in the progression of oral cancer. MDPI 2018-07-10 /pmc/articles/PMC6071146/ /pubmed/29996471 http://dx.doi.org/10.3390/cancers10070228 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Monisha, Javadi
Roy, Nand Kishor
Padmavathi, Ganesan
Banik, Kishore
Bordoloi, Devivasha
Khwairakpam, Amrita Devi
Arfuso, Frank
Chinnathambi, Arunachalam
Alahmadi, Tahani Awad
Alharbi, Sulaiman Ali
Sethi, Gautam
Kumar, Alan Prem
Kunnumakkara, Ajaikumar B.
NGAL is Downregulated in Oral Squamous Cell Carcinoma and Leads to Increased Survival, Proliferation, Migration and Chemoresistance
title NGAL is Downregulated in Oral Squamous Cell Carcinoma and Leads to Increased Survival, Proliferation, Migration and Chemoresistance
title_full NGAL is Downregulated in Oral Squamous Cell Carcinoma and Leads to Increased Survival, Proliferation, Migration and Chemoresistance
title_fullStr NGAL is Downregulated in Oral Squamous Cell Carcinoma and Leads to Increased Survival, Proliferation, Migration and Chemoresistance
title_full_unstemmed NGAL is Downregulated in Oral Squamous Cell Carcinoma and Leads to Increased Survival, Proliferation, Migration and Chemoresistance
title_short NGAL is Downregulated in Oral Squamous Cell Carcinoma and Leads to Increased Survival, Proliferation, Migration and Chemoresistance
title_sort ngal is downregulated in oral squamous cell carcinoma and leads to increased survival, proliferation, migration and chemoresistance
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6071146/
https://www.ncbi.nlm.nih.gov/pubmed/29996471
http://dx.doi.org/10.3390/cancers10070228
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