Journal
JOURNAL OF CANCER
Volume 8, Issue 11, Pages 2088-2096Publisher
IVYSPRING INT PUBL
DOI: 10.7150/jca.19373
Keywords
Malate dehydrogenase; Cancer Metabolism; Lung Cancer
Categories
Funding
- Swedish Research Council (VR-MH)
- Swedish Association for Medical Research (SSMF)
- Malin and Lennart Philipson Foundation
- Ragnar Soderberg Foundation
- Swedish Research Council [VR VR-NT 2012-3045]
- Knut and Alice Wallenbergs Foundation [KAW 2011.0218]
- Jeanssons Foundation
- Alex och Eva Wallstroms Foundation
- Ake Wibergs Foundation
- O. E. och Edla Johanssons Vetenskapliga Foundation
- Magnus Bergwalls Foundation
- Foundation Lars Hiertas Minne
- Foundation Langmanska Kulturfonden
- Karolinska Institute Research grants
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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.
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