Cargando…

Upregulation of pyruvate kinase M2 expression by fatty acid synthase contributes to gemcitabine resistance in pancreatic cancer

Pancreatic cancer has one of the highest mortality rates of all cancer types. Fatty acid synthase (FASN) is a multifunctional protein homodimer that can convert acetyl coenzyme A (CoA) and malonyl-CoA into palmitate, thus regulating lipogenesis. FASN overexpression has also been shown to cause resis...

Descripción completa

Detalles Bibliográficos
Autores principales: Tian, Shenghua, Li, Pingping, Sheng, Shi, Jin, Xin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5777098/
https://www.ncbi.nlm.nih.gov/pubmed/29434927
http://dx.doi.org/10.3892/ol.2017.7598
_version_ 1783294166608904192
author Tian, Shenghua
Li, Pingping
Sheng, Shi
Jin, Xin
author_facet Tian, Shenghua
Li, Pingping
Sheng, Shi
Jin, Xin
author_sort Tian, Shenghua
collection PubMed
description Pancreatic cancer has one of the highest mortality rates of all cancer types. Fatty acid synthase (FASN) is a multifunctional protein homodimer that can convert acetyl coenzyme A (CoA) and malonyl-CoA into palmitate, thus regulating lipogenesis. FASN overexpression has also been shown to cause resistance to gemcitabine, a chemotherapy treatment for pancreatic cancer; however, the mechanism by which this happens is unclear. Analysis of gene expression of FASN and pyruvate kinase M2 (PKM2) in pancreatic cancer was performed using Oncomine microarray gene expression datasets, which demonstrated that FASN and PKM2 were upregulated in pancreatic cancer compared with normal tissue. Specifically, it was demonstrated that FASN enabled the upregulation of PKM2 expression at the mRNA and protein levels, increasing the glucose consumption rate in pancreatic cancer cells. The present study also revealed that decreased levels of FASN reduced resistance to gemcitabine treatment, which was induced by PKM2 overexpression in pancreatic ductal adenocarcinoma cells. Therefore, FASN may represent a novel therapeutic target in pancreatic cancer.
format Online
Article
Text
id pubmed-5777098
institution National Center for Biotechnology Information
language English
publishDate 2018
publisher D.A. Spandidos
record_format MEDLINE/PubMed
spelling pubmed-57770982018-02-12 Upregulation of pyruvate kinase M2 expression by fatty acid synthase contributes to gemcitabine resistance in pancreatic cancer Tian, Shenghua Li, Pingping Sheng, Shi Jin, Xin Oncol Lett Articles Pancreatic cancer has one of the highest mortality rates of all cancer types. Fatty acid synthase (FASN) is a multifunctional protein homodimer that can convert acetyl coenzyme A (CoA) and malonyl-CoA into palmitate, thus regulating lipogenesis. FASN overexpression has also been shown to cause resistance to gemcitabine, a chemotherapy treatment for pancreatic cancer; however, the mechanism by which this happens is unclear. Analysis of gene expression of FASN and pyruvate kinase M2 (PKM2) in pancreatic cancer was performed using Oncomine microarray gene expression datasets, which demonstrated that FASN and PKM2 were upregulated in pancreatic cancer compared with normal tissue. Specifically, it was demonstrated that FASN enabled the upregulation of PKM2 expression at the mRNA and protein levels, increasing the glucose consumption rate in pancreatic cancer cells. The present study also revealed that decreased levels of FASN reduced resistance to gemcitabine treatment, which was induced by PKM2 overexpression in pancreatic ductal adenocarcinoma cells. Therefore, FASN may represent a novel therapeutic target in pancreatic cancer. D.A. Spandidos 2018-02 2017-12-13 /pmc/articles/PMC5777098/ /pubmed/29434927 http://dx.doi.org/10.3892/ol.2017.7598 Text en Copyright: © Tian et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
spellingShingle Articles
Tian, Shenghua
Li, Pingping
Sheng, Shi
Jin, Xin
Upregulation of pyruvate kinase M2 expression by fatty acid synthase contributes to gemcitabine resistance in pancreatic cancer
title Upregulation of pyruvate kinase M2 expression by fatty acid synthase contributes to gemcitabine resistance in pancreatic cancer
title_full Upregulation of pyruvate kinase M2 expression by fatty acid synthase contributes to gemcitabine resistance in pancreatic cancer
title_fullStr Upregulation of pyruvate kinase M2 expression by fatty acid synthase contributes to gemcitabine resistance in pancreatic cancer
title_full_unstemmed Upregulation of pyruvate kinase M2 expression by fatty acid synthase contributes to gemcitabine resistance in pancreatic cancer
title_short Upregulation of pyruvate kinase M2 expression by fatty acid synthase contributes to gemcitabine resistance in pancreatic cancer
title_sort upregulation of pyruvate kinase m2 expression by fatty acid synthase contributes to gemcitabine resistance in pancreatic cancer
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5777098/
https://www.ncbi.nlm.nih.gov/pubmed/29434927
http://dx.doi.org/10.3892/ol.2017.7598
work_keys_str_mv AT tianshenghua upregulationofpyruvatekinasem2expressionbyfattyacidsynthasecontributestogemcitabineresistanceinpancreaticcancer
AT lipingping upregulationofpyruvatekinasem2expressionbyfattyacidsynthasecontributestogemcitabineresistanceinpancreaticcancer
AT shengshi upregulationofpyruvatekinasem2expressionbyfattyacidsynthasecontributestogemcitabineresistanceinpancreaticcancer
AT jinxin upregulationofpyruvatekinasem2expressionbyfattyacidsynthasecontributestogemcitabineresistanceinpancreaticcancer