Abstract:
: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.
journal_name
J Cancerjournal_title
Journal of Cancerauthors
Zhang B,Tornmalm J,Widengren J,Vakifahmetoglu-Norberg H,Norberg Edoi
10.7150/jca.19373subject
Has Abstractpub_date
2017-07-05 00:00:00pages
2088-2096issue
11issn
1837-9664pii
jcav08p2088journal_volume
8pub_type
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