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NADH dehydrogenase complex I is overexpressed in incipient metastatic murine colon cancer cells

Colon cancer is one of the most frequently occurring types of cancers in the world. Primary tumours are treated very efficiently, but the metastatic cases are known to have severe outcomes. Therefore, the aim of the present study was to obtain a greater understanding of the transformation of primary...

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Autores principales: Marquez, Joana, Kratchmarova, Irina, Akimov, Vyacheslav, Unda, Fernando, Ibarretxe, Gaskon, Clerigué, Ariane Schaub, Osinalde, Nerea, Badiola, Iker
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6313061/
https://www.ncbi.nlm.nih.gov/pubmed/30483808
http://dx.doi.org/10.3892/or.2018.6892
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author Marquez, Joana
Kratchmarova, Irina
Akimov, Vyacheslav
Unda, Fernando
Ibarretxe, Gaskon
Clerigué, Ariane Schaub
Osinalde, Nerea
Badiola, Iker
author_facet Marquez, Joana
Kratchmarova, Irina
Akimov, Vyacheslav
Unda, Fernando
Ibarretxe, Gaskon
Clerigué, Ariane Schaub
Osinalde, Nerea
Badiola, Iker
author_sort Marquez, Joana
collection PubMed
description Colon cancer is one of the most frequently occurring types of cancers in the world. Primary tumours are treated very efficiently, but the metastatic cases are known to have severe outcomes. Therefore, the aim of the present study was to obtain a greater understanding of the transformation of primary colon cancer cells into metastatic phenotypes. Small changes in protein expression provoke the metastatic phenotype transformation. More sensitive methods to detect small variations are required. A murine colon cancer cell line with metastatic characteristics in a very early phase was created in order to investigate the first steps of transformation using a murine liver metastasis model. The protein expression patterns of metastatic and non-metastatic cells were compared using the stable isotope labelling by amino acids in cell culture method in combination with mass spectrometry. Quantitative proteomics data indicated that nicotinamide adenine dinucleotide hydride (NADH) dehydrogenase complex I was overexpressed in metastatic cells with respect to non-metastatic cells. Since the NADH dehydrogenase complex catalyses the oxidation of NADH to NAD(+), the functionality of the complex was studied by measuring the amount of NADH. The results revealed that metastatic cells accumulate more NADH and reactive oxygen species. In addition, the mitochondrial membrane potential of metastatic cells was lower than that of non-metastatic cells, indicating that the activity of NADH dehydrogenase and the mitochondrial oxidative chain were decreased in metastatic cells. During the incipient transformation of primary cancer cells, NADH dehydrogenase complex I was overexpressed but then became inactive due to the Warburg effect, which inhibits mitochondrial activity. In the first step of transformation, the high energy demand required in an adverse environment is fulfilled by overexpressing components of the respiratory chain, a fact that should be considered for future anti-metastatic therapies.
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spelling pubmed-63130612019-01-17 NADH dehydrogenase complex I is overexpressed in incipient metastatic murine colon cancer cells Marquez, Joana Kratchmarova, Irina Akimov, Vyacheslav Unda, Fernando Ibarretxe, Gaskon Clerigué, Ariane Schaub Osinalde, Nerea Badiola, Iker Oncol Rep Articles Colon cancer is one of the most frequently occurring types of cancers in the world. Primary tumours are treated very efficiently, but the metastatic cases are known to have severe outcomes. Therefore, the aim of the present study was to obtain a greater understanding of the transformation of primary colon cancer cells into metastatic phenotypes. Small changes in protein expression provoke the metastatic phenotype transformation. More sensitive methods to detect small variations are required. A murine colon cancer cell line with metastatic characteristics in a very early phase was created in order to investigate the first steps of transformation using a murine liver metastasis model. The protein expression patterns of metastatic and non-metastatic cells were compared using the stable isotope labelling by amino acids in cell culture method in combination with mass spectrometry. Quantitative proteomics data indicated that nicotinamide adenine dinucleotide hydride (NADH) dehydrogenase complex I was overexpressed in metastatic cells with respect to non-metastatic cells. Since the NADH dehydrogenase complex catalyses the oxidation of NADH to NAD(+), the functionality of the complex was studied by measuring the amount of NADH. The results revealed that metastatic cells accumulate more NADH and reactive oxygen species. In addition, the mitochondrial membrane potential of metastatic cells was lower than that of non-metastatic cells, indicating that the activity of NADH dehydrogenase and the mitochondrial oxidative chain were decreased in metastatic cells. During the incipient transformation of primary cancer cells, NADH dehydrogenase complex I was overexpressed but then became inactive due to the Warburg effect, which inhibits mitochondrial activity. In the first step of transformation, the high energy demand required in an adverse environment is fulfilled by overexpressing components of the respiratory chain, a fact that should be considered for future anti-metastatic therapies. D.A. Spandidos 2019-02 2018-11-27 /pmc/articles/PMC6313061/ /pubmed/30483808 http://dx.doi.org/10.3892/or.2018.6892 Text en Copyright: © Marquez 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
Marquez, Joana
Kratchmarova, Irina
Akimov, Vyacheslav
Unda, Fernando
Ibarretxe, Gaskon
Clerigué, Ariane Schaub
Osinalde, Nerea
Badiola, Iker
NADH dehydrogenase complex I is overexpressed in incipient metastatic murine colon cancer cells
title NADH dehydrogenase complex I is overexpressed in incipient metastatic murine colon cancer cells
title_full NADH dehydrogenase complex I is overexpressed in incipient metastatic murine colon cancer cells
title_fullStr NADH dehydrogenase complex I is overexpressed in incipient metastatic murine colon cancer cells
title_full_unstemmed NADH dehydrogenase complex I is overexpressed in incipient metastatic murine colon cancer cells
title_short NADH dehydrogenase complex I is overexpressed in incipient metastatic murine colon cancer cells
title_sort nadh dehydrogenase complex i is overexpressed in incipient metastatic murine colon cancer cells
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6313061/
https://www.ncbi.nlm.nih.gov/pubmed/30483808
http://dx.doi.org/10.3892/or.2018.6892
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