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Glutamine regulates ovarian cancer cell migration and invasion through ETS1

Cancer cells are dependent on glutamine for their metabolism and growth. Despite being the most abundant amino acid in the blood, glutamine deprivation occurs in the core of the tumor rendering less access to glutamine to the nearby tumor cells. Tumor cells mostly use the glutamine for mitochondrial...

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Autores principales: Prasad, Parash, Roy, Sib Sankar
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8180613/
https://www.ncbi.nlm.nih.gov/pubmed/34136678
http://dx.doi.org/10.1016/j.heliyon.2021.e07064
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author Prasad, Parash
Roy, Sib Sankar
author_facet Prasad, Parash
Roy, Sib Sankar
author_sort Prasad, Parash
collection PubMed
description Cancer cells are dependent on glutamine for their metabolism and growth. Despite being the most abundant amino acid in the blood, glutamine deprivation occurs in the core of the tumor rendering less access to glutamine to the nearby tumor cells. Tumor cells mostly use the glutamine for mitochondrial oxidative phosphorylation (OXPHOS) to produce energy and the ingredients of the biomass required for the highly proliferating and metastatic ovarian cancer cells. But there is a lack of reports on the regulation of glutamine starvation on metastatic behavior and epithelial to mesenchymal transition (EMT) of ovarian cancer cells. We found that glutamine starvation reduced the migration and invasion properties of the ovarian cancer cells, PA1 and SKOV3. The expression of the invasion-inducing proteins, like matrix metalloproteinases (MMP2 and MMP9), were downregulated upon glutamine starvation. MMP genes are mostly regulated by the ETS1 oncogenic transcription factor in invasive tumor cells. Here we demonstrated the significant involvement of ETS1 on EMT and invasion in glutamine-deprived cells. We have further shown that the regulation of ETS1 expression and nuclear localization upon glutamine starvation is controlled in a cell type-specific manner. In PA1 cells, glutamine-induced ETS1 over-expression is HIF1α-dependent, while in SKOV3, its translocation to the nucleus is regulated through the mTOR pathway. Considering all, our study suggests that glutamine plays a very significant role in migration and invasion in ovarian cancer cells and ETS1 plays a key role in inducing such oncogenic parameters.
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spelling pubmed-81806132021-06-15 Glutamine regulates ovarian cancer cell migration and invasion through ETS1 Prasad, Parash Roy, Sib Sankar Heliyon Research Article Cancer cells are dependent on glutamine for their metabolism and growth. Despite being the most abundant amino acid in the blood, glutamine deprivation occurs in the core of the tumor rendering less access to glutamine to the nearby tumor cells. Tumor cells mostly use the glutamine for mitochondrial oxidative phosphorylation (OXPHOS) to produce energy and the ingredients of the biomass required for the highly proliferating and metastatic ovarian cancer cells. But there is a lack of reports on the regulation of glutamine starvation on metastatic behavior and epithelial to mesenchymal transition (EMT) of ovarian cancer cells. We found that glutamine starvation reduced the migration and invasion properties of the ovarian cancer cells, PA1 and SKOV3. The expression of the invasion-inducing proteins, like matrix metalloproteinases (MMP2 and MMP9), were downregulated upon glutamine starvation. MMP genes are mostly regulated by the ETS1 oncogenic transcription factor in invasive tumor cells. Here we demonstrated the significant involvement of ETS1 on EMT and invasion in glutamine-deprived cells. We have further shown that the regulation of ETS1 expression and nuclear localization upon glutamine starvation is controlled in a cell type-specific manner. In PA1 cells, glutamine-induced ETS1 over-expression is HIF1α-dependent, while in SKOV3, its translocation to the nucleus is regulated through the mTOR pathway. Considering all, our study suggests that glutamine plays a very significant role in migration and invasion in ovarian cancer cells and ETS1 plays a key role in inducing such oncogenic parameters. Elsevier 2021-05-31 /pmc/articles/PMC8180613/ /pubmed/34136678 http://dx.doi.org/10.1016/j.heliyon.2021.e07064 Text en © 2021 The Authors https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Research Article
Prasad, Parash
Roy, Sib Sankar
Glutamine regulates ovarian cancer cell migration and invasion through ETS1
title Glutamine regulates ovarian cancer cell migration and invasion through ETS1
title_full Glutamine regulates ovarian cancer cell migration and invasion through ETS1
title_fullStr Glutamine regulates ovarian cancer cell migration and invasion through ETS1
title_full_unstemmed Glutamine regulates ovarian cancer cell migration and invasion through ETS1
title_short Glutamine regulates ovarian cancer cell migration and invasion through ETS1
title_sort glutamine regulates ovarian cancer cell migration and invasion through ets1
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8180613/
https://www.ncbi.nlm.nih.gov/pubmed/34136678
http://dx.doi.org/10.1016/j.heliyon.2021.e07064
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