NADH dehydrogenase complex I is overexpressed in incipient metastatic murine colon cancer cells
| Autor: | Ariane Schaub Clerigué, Fernando Unda, Irina Kratchmarova, Joana Marquez, Gaskon Ibarretxe, Iker Badiola, Vyacheslav Akimov, Nerea Osinalde |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Male Cancer Research Cell Respiratory chain Oxidative phosphorylation Nicotinamide adenine dinucleotide Nicotinamide adenine dinucleotide hydride dehydrogenase complex I 03 medical and health sciences chemistry.chemical_compound Mice Cell Line Tumor medicine Stable isotope labelling of amino acids in cell culture Animals nicotinamide adenine dinucleotide hydride dehydrogenase complex I Liver metastasis NADH dehydrogenase complex Mice Inbred BALB C Electron Transport Complex I biology Chemistry Liver Neoplasms NADH dehydrogenase NADH Dehydrogenase General Medicine Articles Cell cycle NAD Warburg effect Colon cancer Mitochondria liver metastasis 030104 developmental biology medicine.anatomical_structure Oncology colon cancer Colonic Neoplasms Cancer research biology.protein Reactive Oxygen Species stable isotope labelling of amino acids in cell culture |
| Zdroj: | Oncology Reports Marquez, J, Kratchmarova, I, Akimov, V, Unda, F, Ibarretxe, G, Clerigué, A S, Osinalde, N & Badiola, I 2019, ' NADH dehydrogenase complex I is overexpressed in incipient metastatic murine colon cancer cells ', Oncology Reports, vol. 41, no. 2, pp. 742-752 . https://doi.org/10.3892/or.2018.6892 |
| ISSN: | 1791-2431 1021-335X |
| DOI: | 10.3892/or.2018.6892 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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