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Knockdown of PKM2 Suppresses Tumor Growth and Invasion in Lung Adenocarcinoma

Accumulating evidence shows that activity of the pyruvate kinase M2 (PKM2) isoform is closely related to tumorigenesis. In this study, we investigated the relationship betweenPKM2 expression, tumor invasion, and the prognosis of patients with lung adenocarcinoma. We retrospectively analyzed 65 cases...

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Autores principales: Sun, Hong, Zhu, Anyou, Zhang, Lunjun, Zhang, Jie, Zhong, Zhengrong, Wang, Fengchao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4632765/
https://www.ncbi.nlm.nih.gov/pubmed/26501265
http://dx.doi.org/10.3390/ijms161024574
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author Sun, Hong
Zhu, Anyou
Zhang, Lunjun
Zhang, Jie
Zhong, Zhengrong
Wang, Fengchao
author_facet Sun, Hong
Zhu, Anyou
Zhang, Lunjun
Zhang, Jie
Zhong, Zhengrong
Wang, Fengchao
author_sort Sun, Hong
collection PubMed
description Accumulating evidence shows that activity of the pyruvate kinase M2 (PKM2) isoform is closely related to tumorigenesis. In this study, we investigated the relationship betweenPKM2 expression, tumor invasion, and the prognosis of patients with lung adenocarcinoma. We retrospectively analyzed 65 cases of patients with lung adenocarcinoma who were divided into low and a high expression groups based on PKM2immunohistochemical staining. High PKM2 expression was significantly associated with reduced patient survival. We used small interfering RNA (siRNA) technology to investigate the effect of targeted PKM2-knockout on tumor growth at the cellular level. In vitro, siRNA-mediated PKM2-knockdown significantly inhibited the proliferation, glucose uptake (25%), ATP generation (20%) and fatty acid synthesis of A549 cells, while the mitochondrial respiratory capacity of the cells increased (13%).Western blotting analysis showed that PKM2-knockout significantly inhibited the expression of the glucose transporter GLUT1 and ATP citrate lyase, which is critical for fatty acid synthesis. Further Western blotting analysis showed that PKM2-knockdown inhibited the expression of matrix metalloproteinase 2 (MMP-2) and vascular endothelial growth factor (VEGF), which are important in degradation of the extracellular matrix and angiogenesis, respectively. These observations show that PKM2 activates both glycolysis and lipid synthesis, thereby regulating cell proliferation and invasion. This information is important in elucidating the mechanisms by which PKM2 influences the growth and metastasis of lung adenocarcinoma at the cellular and molecular level, thereby providing the basic data required for the development of PKM2-targeted gene therapy.
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spelling pubmed-46327652015-11-23 Knockdown of PKM2 Suppresses Tumor Growth and Invasion in Lung Adenocarcinoma Sun, Hong Zhu, Anyou Zhang, Lunjun Zhang, Jie Zhong, Zhengrong Wang, Fengchao Int J Mol Sci Article Accumulating evidence shows that activity of the pyruvate kinase M2 (PKM2) isoform is closely related to tumorigenesis. In this study, we investigated the relationship betweenPKM2 expression, tumor invasion, and the prognosis of patients with lung adenocarcinoma. We retrospectively analyzed 65 cases of patients with lung adenocarcinoma who were divided into low and a high expression groups based on PKM2immunohistochemical staining. High PKM2 expression was significantly associated with reduced patient survival. We used small interfering RNA (siRNA) technology to investigate the effect of targeted PKM2-knockout on tumor growth at the cellular level. In vitro, siRNA-mediated PKM2-knockdown significantly inhibited the proliferation, glucose uptake (25%), ATP generation (20%) and fatty acid synthesis of A549 cells, while the mitochondrial respiratory capacity of the cells increased (13%).Western blotting analysis showed that PKM2-knockout significantly inhibited the expression of the glucose transporter GLUT1 and ATP citrate lyase, which is critical for fatty acid synthesis. Further Western blotting analysis showed that PKM2-knockdown inhibited the expression of matrix metalloproteinase 2 (MMP-2) and vascular endothelial growth factor (VEGF), which are important in degradation of the extracellular matrix and angiogenesis, respectively. These observations show that PKM2 activates both glycolysis and lipid synthesis, thereby regulating cell proliferation and invasion. This information is important in elucidating the mechanisms by which PKM2 influences the growth and metastasis of lung adenocarcinoma at the cellular and molecular level, thereby providing the basic data required for the development of PKM2-targeted gene therapy. MDPI 2015-10-15 /pmc/articles/PMC4632765/ /pubmed/26501265 http://dx.doi.org/10.3390/ijms161024574 Text en © 2015 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Sun, Hong
Zhu, Anyou
Zhang, Lunjun
Zhang, Jie
Zhong, Zhengrong
Wang, Fengchao
Knockdown of PKM2 Suppresses Tumor Growth and Invasion in Lung Adenocarcinoma
title Knockdown of PKM2 Suppresses Tumor Growth and Invasion in Lung Adenocarcinoma
title_full Knockdown of PKM2 Suppresses Tumor Growth and Invasion in Lung Adenocarcinoma
title_fullStr Knockdown of PKM2 Suppresses Tumor Growth and Invasion in Lung Adenocarcinoma
title_full_unstemmed Knockdown of PKM2 Suppresses Tumor Growth and Invasion in Lung Adenocarcinoma
title_short Knockdown of PKM2 Suppresses Tumor Growth and Invasion in Lung Adenocarcinoma
title_sort knockdown of pkm2 suppresses tumor growth and invasion in lung adenocarcinoma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4632765/
https://www.ncbi.nlm.nih.gov/pubmed/26501265
http://dx.doi.org/10.3390/ijms161024574
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