Transcription factor NFAT5 contributes to the glycolytic phenotype rewiring and pancreatic cancer progression via transcription of PGK1

Hypoxia and the hypovascular tumor microenvironment are major hallmarks of pancreatic ductal adenocarcinoma (PDAC), in which glycolysis is of great importance to tumor survival and proliferation. There is little research regarding the role of Nuclear Factor of Activated T Cells 5 (NFAT5) in relation...

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Autores principales: Jiang, Yongsheng, He, Ruizhe, Jiang, Yuhong, Liu, Dejun, Tao, Lingye, Yang, Minwei, Lin, Chaoyi, Shen, Yang, Fu, Xueliang, Yang, Jianyu, Li, Jiao, Huo, Yanmiao, Hua, Rong, Liu, Wei, Zhang, Junfeng, Shen, Baiyong, Zhang, Zhigang, Sun, Yongwei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6906509/
https://www.ncbi.nlm.nih.gov/pubmed/31827081
http://dx.doi.org/10.1038/s41419-019-2072-5
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author Jiang, Yongsheng
He, Ruizhe
Jiang, Yuhong
Liu, Dejun
Tao, Lingye
Yang, Minwei
Lin, Chaoyi
Shen, Yang
Fu, Xueliang
Yang, Jianyu
Li, Jiao
Huo, Yanmiao
Hua, Rong
Liu, Wei
Zhang, Junfeng
Shen, Baiyong
Zhang, Zhigang
Sun, Yongwei
author_facet Jiang, Yongsheng
He, Ruizhe
Jiang, Yuhong
Liu, Dejun
Tao, Lingye
Yang, Minwei
Lin, Chaoyi
Shen, Yang
Fu, Xueliang
Yang, Jianyu
Li, Jiao
Huo, Yanmiao
Hua, Rong
Liu, Wei
Zhang, Junfeng
Shen, Baiyong
Zhang, Zhigang
Sun, Yongwei
author_sort Jiang, Yongsheng
collection PubMed
description Hypoxia and the hypovascular tumor microenvironment are major hallmarks of pancreatic ductal adenocarcinoma (PDAC), in which glycolysis is of great importance to tumor survival and proliferation. There is little research regarding the role of Nuclear Factor of Activated T Cells 5 (NFAT5) in relation to carcinoma. Here, we explored the impact of NFAT5 on the biological behavior of PDAC and the underlying mechanism. We demonstrated that NFAT5 was highly expressed in PDAC and was related to poorer prognosis. Knockdown of NFAT5 lead to impaired proliferation of tumor cells caused by an aberrant Warburg effect. Mechanically, phosphoglycerate kinase 1 (PGK-1), which is the first enzyme generating ATP in glycolysis, was verified as a target gene of NFAT5. Over-expression of PGK1 compromised the aberrant oncological behavior caused by knockdown of NFAT5 both in vitro and in vivo. Clinical samples underwent positron emission tomography-computed tomography (PET-CT) examination and KrasG12D/+/Trp53R172H/+/Pdx1-Cre (KPC) mice were collected to support our conclusion.
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spelling pubmed-69065092019-12-12 Transcription factor NFAT5 contributes to the glycolytic phenotype rewiring and pancreatic cancer progression via transcription of PGK1 Jiang, Yongsheng He, Ruizhe Jiang, Yuhong Liu, Dejun Tao, Lingye Yang, Minwei Lin, Chaoyi Shen, Yang Fu, Xueliang Yang, Jianyu Li, Jiao Huo, Yanmiao Hua, Rong Liu, Wei Zhang, Junfeng Shen, Baiyong Zhang, Zhigang Sun, Yongwei Cell Death Dis Article Hypoxia and the hypovascular tumor microenvironment are major hallmarks of pancreatic ductal adenocarcinoma (PDAC), in which glycolysis is of great importance to tumor survival and proliferation. There is little research regarding the role of Nuclear Factor of Activated T Cells 5 (NFAT5) in relation to carcinoma. Here, we explored the impact of NFAT5 on the biological behavior of PDAC and the underlying mechanism. We demonstrated that NFAT5 was highly expressed in PDAC and was related to poorer prognosis. Knockdown of NFAT5 lead to impaired proliferation of tumor cells caused by an aberrant Warburg effect. Mechanically, phosphoglycerate kinase 1 (PGK-1), which is the first enzyme generating ATP in glycolysis, was verified as a target gene of NFAT5. Over-expression of PGK1 compromised the aberrant oncological behavior caused by knockdown of NFAT5 both in vitro and in vivo. Clinical samples underwent positron emission tomography-computed tomography (PET-CT) examination and KrasG12D/+/Trp53R172H/+/Pdx1-Cre (KPC) mice were collected to support our conclusion. Nature Publishing Group UK 2019-12-11 /pmc/articles/PMC6906509/ /pubmed/31827081 http://dx.doi.org/10.1038/s41419-019-2072-5 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
Jiang, Yongsheng
He, Ruizhe
Jiang, Yuhong
Liu, Dejun
Tao, Lingye
Yang, Minwei
Lin, Chaoyi
Shen, Yang
Fu, Xueliang
Yang, Jianyu
Li, Jiao
Huo, Yanmiao
Hua, Rong
Liu, Wei
Zhang, Junfeng
Shen, Baiyong
Zhang, Zhigang
Sun, Yongwei
Transcription factor NFAT5 contributes to the glycolytic phenotype rewiring and pancreatic cancer progression via transcription of PGK1
title Transcription factor NFAT5 contributes to the glycolytic phenotype rewiring and pancreatic cancer progression via transcription of PGK1
title_full Transcription factor NFAT5 contributes to the glycolytic phenotype rewiring and pancreatic cancer progression via transcription of PGK1
title_fullStr Transcription factor NFAT5 contributes to the glycolytic phenotype rewiring and pancreatic cancer progression via transcription of PGK1
title_full_unstemmed Transcription factor NFAT5 contributes to the glycolytic phenotype rewiring and pancreatic cancer progression via transcription of PGK1
title_short Transcription factor NFAT5 contributes to the glycolytic phenotype rewiring and pancreatic cancer progression via transcription of PGK1
title_sort transcription factor nfat5 contributes to the glycolytic phenotype rewiring and pancreatic cancer progression via transcription of pgk1
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6906509/
https://www.ncbi.nlm.nih.gov/pubmed/31827081
http://dx.doi.org/10.1038/s41419-019-2072-5
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