Evidence map›Paper›PMID 37893215›Full record

ArticleBiomedicines2023

Stable Isotope-Assisted Untargeted Metabolomics Identifies ALDH1A1-Driven Erythronate Accumulation in Lung Cancer Cells.

Jie Zhang, Mark A Keibler, Wentao Dong, Jenny Ghelfi, Thekla Cordes, Tamara Kanashova, Arnaud Pailot, Carole L Linster, Gunnar Dittmar, Christian M Metallo and 3 more

Open access · goldAbstract read
In one paragraph

Article in Biomedicines, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
1.0field-weighted citation impact, top 21% 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

7 citing papers in PubMed, 4 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. [Applications and Advances of Metabolomics in Lung Cancer Research].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2025
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors at 6 institutions in 3 countries.

Jie ZhangDepartment of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Mark A KeiblerDepartment of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Wentao DongDepartment of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.ORCID 0000-0001-5490-4265
Jenny GhelfiLuxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, L-4367 Belvaux, Luxembourg.
Thekla CordesLuxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, L-4367 Belvaux, Luxembourg.
Tamara KanashovaMax-Delbrück Center for Molecular Medicine, 13125 Berlin, Germany.
Arnaud PailotLuxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, L-4367 Belvaux, Luxembourg.
Carole L LinsterLuxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, L-4367 Belvaux, Luxembourg.ORCID 0000-0001-7143-0719
Gunnar DittmarMax-Delbrück Center for Molecular Medicine, 13125 Berlin, Germany.ORCID 0000-0003-3647-8623
Christian M MetalloDepartment of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Tim LautenschlaegerDepartment of Radiation Oncology, Wexner Medical Center, Ohio State University, Columbus, OH 43221, USA.
Karsten HillerLuxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, L-4367 Belvaux, Luxembourg.
Gregory StephanopoulosDepartment of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
University of Luxembourg · LUMassachusetts Institute of Technology · USMax Delbrück Center · DEAlnylam Pharmaceuticals (United States) · USSalk Institute for Biological Studies · USThe Ohio State University Wexner Medical Center · US

Funding

Hypoxia-induced Metabolic Changes in CancerR01CA160458 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI ILIOPOULOS, OTHON, STEPHANOPOULOS, GREGORY · 2012 to 2016
$1.6M
Elucidating modulators of hepatic metabolism by quantitative flux analysisR01DK075850 · NIDDK · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI STEPHANOPOULOS, GREGORY · 2006 to 2010
$1.5M
NCI NIH HHS R01 CA160458NIDDK NIH HHS R01 DK075850NIH HHS 1R01CA160458-01A1NIH HHS 1R01DK075850-01
6 · The paper itself

Abstract

Using an untargeted stable isotope-assisted metabolomics approach, we identify erythronate as a metabolite that accumulates in several human cancer cell lines. Erythronate has been reported to be a detoxification product derived from off-target glycolytic metabolism. We use chemical inhibitors and genetic silencing to define the pentose phosphate pathway intermediate erythrose 4-phosphate (E4P) as the starting substrate for erythronate production. However, following enzyme assay-coupled protein fractionation and subsequent proteomics analysis, we identify aldehyde dehydrogenase 1A1 (ALDH1A1) as the predominant contributor to erythrose oxidation to erythronate in cell extracts. Through modulating ALDH1A1 expression in cancer cell lines, we provide additional support. We hence describe a possible alternative route to erythronate production involving the dephosphorylation of E4P to form erythrose, followed by its oxidation by ALDH1A1. Finally, we measure increased erythronate concentrations in tumors relative to adjacent normal tissues from lung cancer patients. These findings suggest the accumulation of erythronate to be an example of metabolic reprogramming in cancer cells, raising the possibility that elevated levels of erythronate may serve as a biomarker of certain types of cancer.

Indexed as

aldehyde dehydrogenase 1A1 (ALDH1A1)cancer metabolismerythronatepentose phosphate pathwayuntargeted metabolomics

Identifiers

PMID37893215
PMCPMC10604529
OpenAlexW4387781168

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.