J Cancer 2017; 8(11):2088-2096. doi:10.7150/jca.19373

Research Paper

Characterization of the Role of the Malate Dehydrogenases to Lung Tumor Cell Survival

Boxi Zhang1, Johan Tornmalm2, Jerker Widengren2, Helin Vakifahmetoglu-Norberg1, Erik Norberg1✉

1. Department of Physiology and Pharmacology, Karolinska Institutet, Nanna Svartz väg 2, SE-171 77, Stockholm, Sweden.
2. Experimental Biomolecular Physics, Department of Applied Physics, Royal Institute of Technology (KTH), AlbaNova University Center, SE-106 91 Stockholm, Sweden.

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Zhang B, Tornmalm J, Widengren J, Vakifahmetoglu-Norberg H, Norberg E. Characterization of the Role of the Malate Dehydrogenases to Lung Tumor Cell Survival. J Cancer 2017; 8(11):2088-2096. doi:10.7150/jca.19373. Available from http://www.jcancer.org/v08p2088.htm

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Cellular compartmentalization of biochemical processes in eukaryotic cells is critical for many functions including shuttling of reducing equivalents across membranes. Although coordination of metabolic flux between different organelles is vital for cell physiology, its impact on tumor cell survival is not well understood. By using an integrative approach, we have dissected the role of the key metabolic enzymes Malate dehydrogenases (MDH1 and MDH2) to the survival of Non-small Cell Lung Carcinomas. Here, we report that while both the MDH1 (cytosolic) and the MDH2 (mitochondrial) enzymes display elevated levels in patients compared to normal counterparts, only high expression of MDH1 is associated with poor prognosis. We further show that the MDH1 enzymatic activity is significantly higher in NSCLC cells than that of MDH2. Accordingly, genetic depletion of MDH1 leads to significantly higher toxicity than depletion of MDH2. These findings provide molecular insights into the metabolic characteristics of the malate isoenzymes and mark MDH1 as a potential therapeutic target in these tumors.

Keywords: Malate dehydrogenase, Cancer Metabolism, Lung Cancer