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Modulation of GLO1 expression affects malignant properties of cells

The energy metabolism of most tumor cells relies on aerobic glycolysis (Warburg effect) characterized by an increased glycolytic flux that is accompanied by the increased formation of the cytotoxic metabolite methylglyoxal (MGO). Consequently, the rate of detoxification of this reactive glycolytic byproduct needs to be increased in order to prevent deleterious effects to the cells. This is brought about by an increased expression of glyoxalase 1 (GLO1) that is the rate-limiting enzyme of the MGO-detoxifying glyoxalase system. Here, we overexpressed GLO1 in HEK 293 cells and silenced it in MCF-7 cells using shRNA. Tumor-related properties of wild type and transformed cells were compared and key glycolytic enzyme activities assessed. Furthermore, the cells were subjected to hypoxic conditions to analyze the impact on cell proliferation and enzyme activities. Our results demonstrate that knockdown of GLO1 in the cancer cells significantly reduced tumor-associated properties such as migration and proliferation, whereas no functional alterations where found by overexpression of GLO1 in HEK 293 cells. In contrast, hypoxia caused inhibition of cell growth of all cells except of those overexpressing GLO1. Altogether, we conclude that GLO1 on one hand is crucial to maintaining tumor characteristics of malignant cells, and, on the other hand, supports malignant transformation of cells in a hypoxic environment when overexpressed.

Identiferoai:union.ndltd.org:DRESDEN/oai:qucosa.de:bsz:15-qucosa-217965
Date25 January 2017
CreatorsHutschenreuther, Antje, Bigl, Marina, Hemdan, Nasr Y. A., Debebe, Tewodros, Gaunitz, Frank, Birkenmeier, Gerd
ContributorsUniversität Leipzig, Medizinische Fakultät, Max-Planck-Institut für Evolutionäre Anthropologie,, Universität Leipzig, Medizinische Fakultät, Bahir Dar University, College of Medicine and Health Sciences, Universität Leipzig, Universitätsklinikum, MDPI,
PublisherUniversitätsbibliothek Leipzig
Source SetsHochschulschriftenserver (HSSS) der SLUB Dresden
LanguageEnglish
Detected LanguageEnglish
Typedoc-type:article
Formatapplication/pdf
SourceInt. J. Mol. Sci. 2016, 17, 2133; doi:10.3390/ijms17122133

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