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The platelet isoform of phosphofructokinase contributes to metabolic reprogramming and maintains cell proliferation in clear cell renal cell carcinoma
Metabolic alterations underlying clear cell renal cell carcinoma (ccRCC) progression include aerobic glycolysis, increased pentose phosphate pathway activity and reduced oxidative phosphorylation. Phosphofructokinase (PFK), a key enzyme of the glycolytic pathway, has L, M, and P isoforms with differ...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5053638/ https://www.ncbi.nlm.nih.gov/pubmed/27049827 http://dx.doi.org/10.18632/oncotarget.8382 |
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author | Wang, Jun Zhang, Ping Zhong, Jie Tan, Mingyue Ge, Jifu Tao, Le Li, Yakui Zhu, Yemin Wu, Lifang Qiu, Jianxin Tong, Xuemei |
author_facet | Wang, Jun Zhang, Ping Zhong, Jie Tan, Mingyue Ge, Jifu Tao, Le Li, Yakui Zhu, Yemin Wu, Lifang Qiu, Jianxin Tong, Xuemei |
author_sort | Wang, Jun |
collection | PubMed |
description | Metabolic alterations underlying clear cell renal cell carcinoma (ccRCC) progression include aerobic glycolysis, increased pentose phosphate pathway activity and reduced oxidative phosphorylation. Phosphofructokinase (PFK), a key enzyme of the glycolytic pathway, has L, M, and P isoforms with different tissue distributions. The mRNA level of the platelet isoform of phosphofructokinase (PFKP) is reported to be up-regulated in ccRCC patients. However, it remains unclear whether PFKP plays an important role in promoting aerobic glycolysis and macromolecular biosynthesis to support cell proliferation in ccRCC. Here we found that the up-regulated PFKP became the predominant isoform of PFK in human ccRCC. Suppression of PFKP not only impaired cell proliferation by inducing cell cycle arrest and apoptosis, but also led to decreased glycolysis, pentose phosphate pathway and nucleotide biosynthesis, accompanied by activated tricarboxylic acid cycle in ccRCC cells. Moreover, we found that p53 activation contributed to cell proliferation and metabolic defects induced by PFKP knockdown in ccRCC cells. Furthermore, suppression of PFKP led to reduced ccRCC tumor growth in vivo. Our data indicate that PFKP not only is required for metabolic reprogramming and maintaining cell proliferation, but also may provide us with a valid target for anti-renal cancer pharmaceutical agents. |
format | Online Article Text |
id | pubmed-5053638 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-50536382016-10-12 The platelet isoform of phosphofructokinase contributes to metabolic reprogramming and maintains cell proliferation in clear cell renal cell carcinoma Wang, Jun Zhang, Ping Zhong, Jie Tan, Mingyue Ge, Jifu Tao, Le Li, Yakui Zhu, Yemin Wu, Lifang Qiu, Jianxin Tong, Xuemei Oncotarget Research Paper Metabolic alterations underlying clear cell renal cell carcinoma (ccRCC) progression include aerobic glycolysis, increased pentose phosphate pathway activity and reduced oxidative phosphorylation. Phosphofructokinase (PFK), a key enzyme of the glycolytic pathway, has L, M, and P isoforms with different tissue distributions. The mRNA level of the platelet isoform of phosphofructokinase (PFKP) is reported to be up-regulated in ccRCC patients. However, it remains unclear whether PFKP plays an important role in promoting aerobic glycolysis and macromolecular biosynthesis to support cell proliferation in ccRCC. Here we found that the up-regulated PFKP became the predominant isoform of PFK in human ccRCC. Suppression of PFKP not only impaired cell proliferation by inducing cell cycle arrest and apoptosis, but also led to decreased glycolysis, pentose phosphate pathway and nucleotide biosynthesis, accompanied by activated tricarboxylic acid cycle in ccRCC cells. Moreover, we found that p53 activation contributed to cell proliferation and metabolic defects induced by PFKP knockdown in ccRCC cells. Furthermore, suppression of PFKP led to reduced ccRCC tumor growth in vivo. Our data indicate that PFKP not only is required for metabolic reprogramming and maintaining cell proliferation, but also may provide us with a valid target for anti-renal cancer pharmaceutical agents. Impact Journals LLC 2016-03-25 /pmc/articles/PMC5053638/ /pubmed/27049827 http://dx.doi.org/10.18632/oncotarget.8382 Text en Copyright: © 2016 Wang et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper Wang, Jun Zhang, Ping Zhong, Jie Tan, Mingyue Ge, Jifu Tao, Le Li, Yakui Zhu, Yemin Wu, Lifang Qiu, Jianxin Tong, Xuemei The platelet isoform of phosphofructokinase contributes to metabolic reprogramming and maintains cell proliferation in clear cell renal cell carcinoma |
title | The platelet isoform of phosphofructokinase contributes to metabolic reprogramming and maintains cell proliferation in clear cell renal cell carcinoma |
title_full | The platelet isoform of phosphofructokinase contributes to metabolic reprogramming and maintains cell proliferation in clear cell renal cell carcinoma |
title_fullStr | The platelet isoform of phosphofructokinase contributes to metabolic reprogramming and maintains cell proliferation in clear cell renal cell carcinoma |
title_full_unstemmed | The platelet isoform of phosphofructokinase contributes to metabolic reprogramming and maintains cell proliferation in clear cell renal cell carcinoma |
title_short | The platelet isoform of phosphofructokinase contributes to metabolic reprogramming and maintains cell proliferation in clear cell renal cell carcinoma |
title_sort | platelet isoform of phosphofructokinase contributes to metabolic reprogramming and maintains cell proliferation in clear cell renal cell carcinoma |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5053638/ https://www.ncbi.nlm.nih.gov/pubmed/27049827 http://dx.doi.org/10.18632/oncotarget.8382 |
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