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Targeting of lipid metabolism with a metabolic inhibitor cocktail eradicates peritoneal metastases in ovarian cancer cells
Ovarian cancer is an intra-abdominal tumor in which the presence of ascites facilitates metastatic dissemination, and associated with poor prognosis. However, the significance of metabolic alterations in ovarian cancer cells in the ascites microenvironment remains unclear. Here we show ovarian cance...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6668395/ https://www.ncbi.nlm.nih.gov/pubmed/31372520 http://dx.doi.org/10.1038/s42003-019-0508-1 |
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author | Chen, Rain R. Yung, Mingo M. H. Xuan, Yang Zhan, Shijie Leung, Leanne L. Liang, Rachel R. Leung, Thomas H. Y. Yang, Huijuan Xu, Dakang Sharma, Rakesh Chan, Karen K. L. Ngu, Siew-Fei Ngan, Hextan Y. S. Chan, David W. |
author_facet | Chen, Rain R. Yung, Mingo M. H. Xuan, Yang Zhan, Shijie Leung, Leanne L. Liang, Rachel R. Leung, Thomas H. Y. Yang, Huijuan Xu, Dakang Sharma, Rakesh Chan, Karen K. L. Ngu, Siew-Fei Ngan, Hextan Y. S. Chan, David W. |
author_sort | Chen, Rain R. |
collection | PubMed |
description | Ovarian cancer is an intra-abdominal tumor in which the presence of ascites facilitates metastatic dissemination, and associated with poor prognosis. However, the significance of metabolic alterations in ovarian cancer cells in the ascites microenvironment remains unclear. Here we show ovarian cancer cells exhibited increased aggressiveness in ascites microenvironment via reprogramming of lipid metabolism. High lipid metabolic activities are found in ovarian cancer cells when cultured in the ascites microenvironment, indicating a metabolic shift from aerobic glycolysis to β-oxidation and lipogenesis. The reduced AMP-activated protein kinase (AMPK) activity due to the feedback effect of high energy production led to the activation of its downstream signaling, which in turn, enhanced the cancer growth. The combined treatment of low toxic AMPK activators, the transforming growth factor beta-activated kinase 1 (TAK1) and fatty acid synthase (FASN) inhibitors synergistically impair oncogenic augmentation of ovarian cancer. Collectively, targeting lipid metabolism signaling axis impede ovarian cancer peritoneal metastases. |
format | Online Article Text |
id | pubmed-6668395 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-66683952019-08-01 Targeting of lipid metabolism with a metabolic inhibitor cocktail eradicates peritoneal metastases in ovarian cancer cells Chen, Rain R. Yung, Mingo M. H. Xuan, Yang Zhan, Shijie Leung, Leanne L. Liang, Rachel R. Leung, Thomas H. Y. Yang, Huijuan Xu, Dakang Sharma, Rakesh Chan, Karen K. L. Ngu, Siew-Fei Ngan, Hextan Y. S. Chan, David W. Commun Biol Article Ovarian cancer is an intra-abdominal tumor in which the presence of ascites facilitates metastatic dissemination, and associated with poor prognosis. However, the significance of metabolic alterations in ovarian cancer cells in the ascites microenvironment remains unclear. Here we show ovarian cancer cells exhibited increased aggressiveness in ascites microenvironment via reprogramming of lipid metabolism. High lipid metabolic activities are found in ovarian cancer cells when cultured in the ascites microenvironment, indicating a metabolic shift from aerobic glycolysis to β-oxidation and lipogenesis. The reduced AMP-activated protein kinase (AMPK) activity due to the feedback effect of high energy production led to the activation of its downstream signaling, which in turn, enhanced the cancer growth. The combined treatment of low toxic AMPK activators, the transforming growth factor beta-activated kinase 1 (TAK1) and fatty acid synthase (FASN) inhibitors synergistically impair oncogenic augmentation of ovarian cancer. Collectively, targeting lipid metabolism signaling axis impede ovarian cancer peritoneal metastases. Nature Publishing Group UK 2019-07-31 /pmc/articles/PMC6668395/ /pubmed/31372520 http://dx.doi.org/10.1038/s42003-019-0508-1 Text en © The Author(s) 2019 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 Chen, Rain R. Yung, Mingo M. H. Xuan, Yang Zhan, Shijie Leung, Leanne L. Liang, Rachel R. Leung, Thomas H. Y. Yang, Huijuan Xu, Dakang Sharma, Rakesh Chan, Karen K. L. Ngu, Siew-Fei Ngan, Hextan Y. S. Chan, David W. Targeting of lipid metabolism with a metabolic inhibitor cocktail eradicates peritoneal metastases in ovarian cancer cells |
title | Targeting of lipid metabolism with a metabolic inhibitor cocktail eradicates peritoneal metastases in ovarian cancer cells |
title_full | Targeting of lipid metabolism with a metabolic inhibitor cocktail eradicates peritoneal metastases in ovarian cancer cells |
title_fullStr | Targeting of lipid metabolism with a metabolic inhibitor cocktail eradicates peritoneal metastases in ovarian cancer cells |
title_full_unstemmed | Targeting of lipid metabolism with a metabolic inhibitor cocktail eradicates peritoneal metastases in ovarian cancer cells |
title_short | Targeting of lipid metabolism with a metabolic inhibitor cocktail eradicates peritoneal metastases in ovarian cancer cells |
title_sort | targeting of lipid metabolism with a metabolic inhibitor cocktail eradicates peritoneal metastases in ovarian cancer cells |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6668395/ https://www.ncbi.nlm.nih.gov/pubmed/31372520 http://dx.doi.org/10.1038/s42003-019-0508-1 |
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