Evidence map›Paper›PMID 30355481›Full record

ArticleCell reports2018

Oncogenic R132 IDH1 Mutations Limit NADPH for De Novo Lipogenesis through (D)2-Hydroxyglutarate Production in Fibrosarcoma Sells.

Mehmet G Badur, Thangaselvam Muthusamy, Seth J Parker, Shenghong Ma, Samuel K McBrayer, Thekla Cordes, Jose H Magana, Kun-Liang Guan, Christian M Metallo

Erratum issuedOpen access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 49 papers.

0numbers the graph read from it
0cells of the map it votes in
49citing papers in PubMed
2.5field-weighted citation impact, top 10% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

49 citing papers in PubMed, 83 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. International journal of molecular sciences · 2025
    Article
  5. Article
  6. Review
  7. Article
  8. Article
  9. IDH mutant high-grade gliomas.Frontiers in molecular neuroscience · 2025
    Review
  10. Review
  11. Article
  12. Review
  13. Tracing the Diverse Paths of One-Carbon Metabolism in Cancer and Beyond.Cold Spring Harbor perspectives in medicine · 2024
    Review
  14. Article
  15. Review
  16. Review
  17. Article
  18. Article
  19. Review
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors at 2 institutions in 1 country.

Mehmet G BadurDepartment of Bioengineering, University of California, San Diego, La Jolla, CA 92037, USA.
Thangaselvam MuthusamyDepartment of Bioengineering, University of California, San Diego, La Jolla, CA 92037, USA.
Seth J ParkerDepartment of Bioengineering, University of California, San Diego, La Jolla, CA 92037, USA.
Shenghong MaDepartment of Pharmacology, University of California, San Diego, La Jolla, CA 92037, USA; Moores Cancer Center, University of California, San Diego, La Jolla, CA 92037, USA.
Samuel K McBrayerDepartment of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02115, USA.
Thekla CordesDepartment of Bioengineering, University of California, San Diego, La Jolla, CA 92037, USA.
Jose H MaganaDepartment of Bioengineering, University of California, San Diego, La Jolla, CA 92037, USA.
Kun-Liang GuanDepartment of Pharmacology, University of California, San Diego, La Jolla, CA 92037, USA; Moores Cancer Center, University of California, San Diego, La Jolla, CA 92037, USA.
Christian M MetalloDepartment of Bioengineering, University of California, San Diego, La Jolla, CA 92037, USA; Moores Cancer Center, University of California, San Diego, La Jolla, CA 92037, USA. Electronic address: cmetallo@ucsd.edu.
University of California, San Diego · USHarvard University · US

Funding

The mTOR and Hippo pathway in cell growth and cancerR35CA196878 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI GUAN, KUN-LIANG · 2015 to 2019
$4.0M
Exploiting Metabloic Defects in Tumors with Mutant IDH1 and IDH2R01CA188652 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI METALLO, CHRISTIAN MICHAEL · 2014 to 2018
$1.6M
NCI NIH HHS R01 CA188652NCI NIH HHS R35 CA196878
6 · The paper itself

Abstract

Neomorphic mutations in NADP-dependent isocitrate dehydrogenases (IDH1 and IDH2) contribute to tumorigenesis in several cancers. Although significant research has focused on the hypermethylation phenotypes associated with (D)2-hydroxyglutarate (D2HG) accumulation, the metabolic consequences of these mutations may also provide therapeutic opportunities. Here we apply flux-based approaches to genetically engineered cell lines with an endogenous IDH1 mutation to examine the metabolic impacts of increased D2HG production and altered IDH flux as a function of IDH1 mutation or expression. D2HG synthesis in IDH1-mutant cells consumes NADPH at rates similar to de novo lipogenesis. IDH1-mutant cells exhibit increased dependence on exogenous lipid sources for in vitro growth, as removal of medium lipids slows growth more dramatically in IDH1-mutant cells compared with those expressing wild-type or enzymatically inactive alleles. NADPH regeneration may be limiting for lipogenesis and potentially redox homeostasis in IDH1-mutant cells, highlighting critical links between cellular biosynthesis and redox metabolism.

Indexed as

LipogenesisOncogenesCell Line, TumorCytosolFibrosarcomaGlutaratesHumansIsocitrate DehydrogenaseLipidsMutationNADPalpha-hydroxyglutarateGlutaratesIDH1 protein, humanIsocitrate DehydrogenaseLipidsNADP2-hydroxyglutrate (2HG)cancerdeuteriumIDH1IDH2metabolic flux analysismetabolismNADPHredox metabolism

Identifiers

PMID30355481
PMCPMC6613636
OpenAlexW2897144256

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.