Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Characterization of the role of the Malate dehydrogenases to lung tumor cell survival
KTH, School of Engineering Sciences (SCI), Applied Physics, Experimental Biomolecular Physics.
KTH, School of Engineering Sciences (SCI), Applied Physics, Experimental Biomolecular Physics.
Show others and affiliations
2017 (English)In: Journal of Cancer, ISSN 1837-9664, E-ISSN 1837-9664, Vol. 8, no 11, article id 19373Article in journal (Refereed) Published
Abstract [en]

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 Nonsmall 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.

Place, publisher, year, edition, pages
Ivyspring International Publisher , 2017. Vol. 8, no 11, article id 19373
Keywords [en]
Cancer Metabolism, Lung Cancer, Malate dehydrogenase
National Category
Cancer and Oncology
Identifiers
URN: urn:nbn:se:kth:diva-211854DOI: 10.7150/jca.19373ISI: 000406938500019Scopus ID: 2-s2.0-85025125739OAI: oai:DiVA.org:kth-211854DiVA, id: diva2:1131562
Funder
Swedish Research Council, VR-NT 2012-3045Swedish Society for Medical Research (SSMF)Ragnar Söderbergs stiftelseKnut and Alice Wallenberg Foundation, KAW 2011.0218Åke Wiberg FoundationStiftelsen Längmanska kulturfondenLars Hierta Memorial Foundation
Note

QC 20170815

Available from: 2017-08-15 Created: 2017-08-15 Last updated: 2017-11-29Bibliographically approved

Open Access in DiVA

No full text in DiVA

Other links

Publisher's full textScopus

Search in DiVA

By author/editor
Tornmalm, JohanWidengren, Jerker
By organisation
Experimental Biomolecular Physics
In the same journal
Journal of Cancer
Cancer and Oncology

Search outside of DiVA

GoogleGoogle Scholar

doi
urn-nbn

Altmetric score

doi
urn-nbn
Total: 28 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf