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Inactivation of HMGCL promotes proliferation and metastasis of nasopharyngeal carcinoma by suppressing oxidative stress

Altered metabolism is considered as a hallmark of cancer. Here we investigated expression of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) 2 lyase (HMGCL), an essential enzyme in ketogenesis, which produces ketone bodies by the breakdown of fatty acids to supply energy, in nasopharyngeal carcinoma...

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Autores principales: Luo, Wenqi, Qin, Liting, Li, Bo, Liao, Zhipeng, Liang, Jiezhen, Xiao, Xiling, Xiao, Xue, Mo, Yingxi, Huang, Guangwu, Zhang, Zhe, Zhou, Xiaoying, Li, Ping
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5607293/
https://www.ncbi.nlm.nih.gov/pubmed/28931870
http://dx.doi.org/10.1038/s41598-017-11025-2
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author Luo, Wenqi
Qin, Liting
Li, Bo
Liao, Zhipeng
Liang, Jiezhen
Xiao, Xiling
Xiao, Xue
Mo, Yingxi
Huang, Guangwu
Zhang, Zhe
Zhou, Xiaoying
Li, Ping
author_facet Luo, Wenqi
Qin, Liting
Li, Bo
Liao, Zhipeng
Liang, Jiezhen
Xiao, Xiling
Xiao, Xue
Mo, Yingxi
Huang, Guangwu
Zhang, Zhe
Zhou, Xiaoying
Li, Ping
author_sort Luo, Wenqi
collection PubMed
description Altered metabolism is considered as a hallmark of cancer. Here we investigated expression of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) 2 lyase (HMGCL), an essential enzyme in ketogenesis, which produces ketone bodies by the breakdown of fatty acids to supply energy, in nasopharyngeal carcinoma (NPC). The expression of HMGCL was silenced in NPC tissue. Downregulation of HMGCL in NPC was associated with low intracellular β-hydroxybutyrate (β-HB) production, thereby reducing reactive oxygen species (ROS) generation. Ectopic expression of HMGCL restored β-HB level, associated with suppressed proliferation and colony formation of NPC cells in vitro and decreased tumorigenicity in vivo. HMGCL suppressed the migration and invasion of NPC cells in vitro via mesenchymal-epithelial transition. Furthermore, extracellular β-HB supply suppressed the proliferation and migration of NPC cells. Both intra- and extracellular β-HB exerting a suppressive role in NPC depends on ROS generation. Ketogenesis may be impaired in NPC cells due to lack of HMGCL expression, suggesting that it may be a promising target in NPC therapy.
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spelling pubmed-56072932017-09-24 Inactivation of HMGCL promotes proliferation and metastasis of nasopharyngeal carcinoma by suppressing oxidative stress Luo, Wenqi Qin, Liting Li, Bo Liao, Zhipeng Liang, Jiezhen Xiao, Xiling Xiao, Xue Mo, Yingxi Huang, Guangwu Zhang, Zhe Zhou, Xiaoying Li, Ping Sci Rep Article Altered metabolism is considered as a hallmark of cancer. Here we investigated expression of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) 2 lyase (HMGCL), an essential enzyme in ketogenesis, which produces ketone bodies by the breakdown of fatty acids to supply energy, in nasopharyngeal carcinoma (NPC). The expression of HMGCL was silenced in NPC tissue. Downregulation of HMGCL in NPC was associated with low intracellular β-hydroxybutyrate (β-HB) production, thereby reducing reactive oxygen species (ROS) generation. Ectopic expression of HMGCL restored β-HB level, associated with suppressed proliferation and colony formation of NPC cells in vitro and decreased tumorigenicity in vivo. HMGCL suppressed the migration and invasion of NPC cells in vitro via mesenchymal-epithelial transition. Furthermore, extracellular β-HB supply suppressed the proliferation and migration of NPC cells. Both intra- and extracellular β-HB exerting a suppressive role in NPC depends on ROS generation. Ketogenesis may be impaired in NPC cells due to lack of HMGCL expression, suggesting that it may be a promising target in NPC therapy. Nature Publishing Group UK 2017-09-20 /pmc/articles/PMC5607293/ /pubmed/28931870 http://dx.doi.org/10.1038/s41598-017-11025-2 Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Luo, Wenqi
Qin, Liting
Li, Bo
Liao, Zhipeng
Liang, Jiezhen
Xiao, Xiling
Xiao, Xue
Mo, Yingxi
Huang, Guangwu
Zhang, Zhe
Zhou, Xiaoying
Li, Ping
Inactivation of HMGCL promotes proliferation and metastasis of nasopharyngeal carcinoma by suppressing oxidative stress
title Inactivation of HMGCL promotes proliferation and metastasis of nasopharyngeal carcinoma by suppressing oxidative stress
title_full Inactivation of HMGCL promotes proliferation and metastasis of nasopharyngeal carcinoma by suppressing oxidative stress
title_fullStr Inactivation of HMGCL promotes proliferation and metastasis of nasopharyngeal carcinoma by suppressing oxidative stress
title_full_unstemmed Inactivation of HMGCL promotes proliferation and metastasis of nasopharyngeal carcinoma by suppressing oxidative stress
title_short Inactivation of HMGCL promotes proliferation and metastasis of nasopharyngeal carcinoma by suppressing oxidative stress
title_sort inactivation of hmgcl promotes proliferation and metastasis of nasopharyngeal carcinoma by suppressing oxidative stress
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5607293/
https://www.ncbi.nlm.nih.gov/pubmed/28931870
http://dx.doi.org/10.1038/s41598-017-11025-2
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