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Deregulation of lysophosphatidic acid metabolism in oral cancer promotes cell migration via the up-regulation of COX-2
Oral squamous cell carcinoma (OSCC) is the sixth most common cancer worldwide and accounts for 300,000 new cases yearly. The five-year survival rate is approximately 50% and the major challenges to improving patient prognosis include late presentation, treatment resistance, second primary tumours an...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
PeerJ Inc.
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7666559/ https://www.ncbi.nlm.nih.gov/pubmed/33240646 http://dx.doi.org/10.7717/peerj.10328 |
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author | Abdul Rahman, Mariati Tan, May Leng Johnson, Steven P. Hollows, Robert J. Chai, Wen Lin Mansell, Jason P. Yap, Lee Fah Paterson, Ian C. |
author_facet | Abdul Rahman, Mariati Tan, May Leng Johnson, Steven P. Hollows, Robert J. Chai, Wen Lin Mansell, Jason P. Yap, Lee Fah Paterson, Ian C. |
author_sort | Abdul Rahman, Mariati |
collection | PubMed |
description | Oral squamous cell carcinoma (OSCC) is the sixth most common cancer worldwide and accounts for 300,000 new cases yearly. The five-year survival rate is approximately 50% and the major challenges to improving patient prognosis include late presentation, treatment resistance, second primary tumours and the lack of targeted therapies. Therefore, there is a compelling need to develop novel therapeutic strategies. In this study, we have examined the effect of lysophosphatidic acid (LPA) on OSCC cell migration, invasion and response to radiation, and investigated the contribution of cyclooxygenase-2 (COX-2) in mediating the tumour promoting effects of LPA. Using the TCGA data set, we show that the expression of the lipid phosphate phosphatases (LPP), LPP1 and LPP3, was significantly down-regulated in OSCC tissues. There was no significant difference in the expression of the ENPP2 gene, which encodes for the enzyme autotaxin (ATX) that produces LPA, between OSCCs and control tissues but ENPP2 levels were elevated in a subgroup of OSCCs. To explore the phenotypic effects of LPA, we treated OSCC cell lines with LPA and showed that the lipid enhanced migration and invasion as well as suppressed the response of the cells to irradiation. We also show that LPA increased COX-2 mRNA and protein levels in OSCC cell lines and inhibition of COX-2 activity with the COX-2 inhibitor, NS398, attenuated LPA-induced OSCC cell migration. Collectively, our data show for the first time that COX-2 mediates some of the pro-tumorigenic effects of LPA in OSCC and identifies the ATX-LPP-LPA-COX-2 pathway as a potential therapeutic target for this disease. |
format | Online Article Text |
id | pubmed-7666559 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | PeerJ Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-76665592020-11-24 Deregulation of lysophosphatidic acid metabolism in oral cancer promotes cell migration via the up-regulation of COX-2 Abdul Rahman, Mariati Tan, May Leng Johnson, Steven P. Hollows, Robert J. Chai, Wen Lin Mansell, Jason P. Yap, Lee Fah Paterson, Ian C. PeerJ Biochemistry Oral squamous cell carcinoma (OSCC) is the sixth most common cancer worldwide and accounts for 300,000 new cases yearly. The five-year survival rate is approximately 50% and the major challenges to improving patient prognosis include late presentation, treatment resistance, second primary tumours and the lack of targeted therapies. Therefore, there is a compelling need to develop novel therapeutic strategies. In this study, we have examined the effect of lysophosphatidic acid (LPA) on OSCC cell migration, invasion and response to radiation, and investigated the contribution of cyclooxygenase-2 (COX-2) in mediating the tumour promoting effects of LPA. Using the TCGA data set, we show that the expression of the lipid phosphate phosphatases (LPP), LPP1 and LPP3, was significantly down-regulated in OSCC tissues. There was no significant difference in the expression of the ENPP2 gene, which encodes for the enzyme autotaxin (ATX) that produces LPA, between OSCCs and control tissues but ENPP2 levels were elevated in a subgroup of OSCCs. To explore the phenotypic effects of LPA, we treated OSCC cell lines with LPA and showed that the lipid enhanced migration and invasion as well as suppressed the response of the cells to irradiation. We also show that LPA increased COX-2 mRNA and protein levels in OSCC cell lines and inhibition of COX-2 activity with the COX-2 inhibitor, NS398, attenuated LPA-induced OSCC cell migration. Collectively, our data show for the first time that COX-2 mediates some of the pro-tumorigenic effects of LPA in OSCC and identifies the ATX-LPP-LPA-COX-2 pathway as a potential therapeutic target for this disease. PeerJ Inc. 2020-11-11 /pmc/articles/PMC7666559/ /pubmed/33240646 http://dx.doi.org/10.7717/peerj.10328 Text en ©2020 Abdul Rahman et al. https://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, reproduction and adaptation in any medium and for any purpose provided that it is properly attributed. For attribution, the original author(s), title, publication source (PeerJ) and either DOI or URL of the article must be cited. |
spellingShingle | Biochemistry Abdul Rahman, Mariati Tan, May Leng Johnson, Steven P. Hollows, Robert J. Chai, Wen Lin Mansell, Jason P. Yap, Lee Fah Paterson, Ian C. Deregulation of lysophosphatidic acid metabolism in oral cancer promotes cell migration via the up-regulation of COX-2 |
title | Deregulation of lysophosphatidic acid metabolism in oral cancer promotes cell migration via the up-regulation of COX-2 |
title_full | Deregulation of lysophosphatidic acid metabolism in oral cancer promotes cell migration via the up-regulation of COX-2 |
title_fullStr | Deregulation of lysophosphatidic acid metabolism in oral cancer promotes cell migration via the up-regulation of COX-2 |
title_full_unstemmed | Deregulation of lysophosphatidic acid metabolism in oral cancer promotes cell migration via the up-regulation of COX-2 |
title_short | Deregulation of lysophosphatidic acid metabolism in oral cancer promotes cell migration via the up-regulation of COX-2 |
title_sort | deregulation of lysophosphatidic acid metabolism in oral cancer promotes cell migration via the up-regulation of cox-2 |
topic | Biochemistry |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7666559/ https://www.ncbi.nlm.nih.gov/pubmed/33240646 http://dx.doi.org/10.7717/peerj.10328 |
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