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

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 Cancer

journal_title

Journal of Cancer

authors

Zhang B,Tornmalm J,Widengren J,Vakifahmetoglu-Norberg H,Norberg E

doi

10.7150/jca.19373

subject

Has Abstract

pub_date

2017-07-05 00:00:00

pages

2088-2096

issue

11

issn

1837-9664

pii

jcav08p2088

journal_volume

8

pub_type

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