Evidence map›Paper›PMID 41593071›Full record

ArticleNature communications2026

Ether lipids influence cancer cell fate by modulating iron uptake.

Ryan P Mansell, Sebastian Müller, Jia-Shu Yang, Sarah Innes-Gold, Sunny Das, Ferenc Reinhardt, Kim Janina Sigmund, Vaishnavi V Phadnis, Zhengpeng Wan, Jillian Stark and 21 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
–field-weighted citation impact
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

14 citing papers in PubMed.

  1. Article
  2. Review
  3. Review
  4. Article
  5. Article
  6. Article
  7. Article
  8. Review
  9. Article
  10. Review
  11. Article
  12. Iron and Cancer.Advances in experimental medicine and biology · 2025
    Review
  13. Article
  14. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

31 authors.

Ryan P Mansell *Department of Biology, MIT, Cambridge, MA, 02139, USA.
Sebastian Müller *Institut Curie, CNRS, INSERM, PSL Research University, Equipe Labellisée Ligue Contre le Cancer, Paris, 75005, France.ORCID http://orcid.org/0000-0002-3423-5364
Jia-Shu YangDivision of Rheumatology, Inflammation and Immunity, Brigham and Women's Hospital, and Dept. of Medicine, Harvard Medical School, Boston, MA, 02115, USA.
Sarah Innes-GoldDepartment of Chemistry and Chemical Biology, Harvard University, Cambridge, MA, 02138, USA.
Sunny DasWhitehead Institute for Biomedical Research, Cambridge, MA, 02142, USA.ORCID http://orcid.org/0000-0003-1154-3441
Ferenc ReinhardtWhitehead Institute for Biomedical Research, Cambridge, MA, 02142, USA.
Kim Janina SigmundWhitehead Institute for Biomedical Research, Cambridge, MA, 02142, USA.
Vaishnavi V PhadnisDepartment of Biology, MIT, Cambridge, MA, 02139, USA.ORCID http://orcid.org/0000-0001-8452-8512
Zhengpeng WanDepartment of Biological Engineering, MIT, Cambridge, MA, 02139, USA.ORCID http://orcid.org/0000-0001-5626-7722
Jillian StarkDepartment of Biology, MIT, Cambridge, MA, 02139, USA.
Daehee HwangDepartment of Biology, MIT, Cambridge, MA, 02139, USA.
Fabien SindikubwaboInstitut Curie, CNRS, INSERM, PSL Research University, Equipe Labellisée Ligue Contre le Cancer, Paris, 75005, France.ORCID http://orcid.org/0000-0002-9381-6302
Laurène SyxInstitut Curie, INSERM, Mines ParisTech, Paris, 75005, France.ORCID http://orcid.org/0009-0005-5749-0738
Nicolas ServantInstitut Curie, INSERM, Mines ParisTech, Paris, 75005, France.ORCID http://orcid.org/0000-0003-1678-7410
Elinor Ng EatonWhitehead Institute for Biomedical Research, Cambridge, MA, 02142, USA.
Julio L SampaioInstitut Curie, CurieCoreTech Metabolomics and Lipidomics platform, Paris, 75005, France.
George W BellWhitehead Institute for Biomedical Research, Cambridge, MA, 02142, USA.ORCID http://orcid.org/0000-0001-6826-2507
Prathapan ThiruWhitehead Institute for Biomedical Research, Cambridge, MA, 02142, USA.
Amartya ViravalliDepartment of Chemical Engineering and Materials Science, University of Minnesota, Minneapolis, MN, 55455, USA.
Amy DeikThe Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.ORCID http://orcid.org/0000-0002-9687-0953
Clary B ClishThe Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.ORCID http://orcid.org/0000-0001-8259-9245
Paula T HammondKoch Institute for Integrative Cancer Research, MIT, Cambridge, MA, 02139, USA.ORCID http://orcid.org/0000-0002-9835-192X
Roger D KammDepartment of Biological Engineering, MIT, Cambridge, MA, 02139, USA.ORCID http://orcid.org/0000-0002-7232-304X
Adam E CohenDepartment of Chemistry and Chemical Biology, Harvard University, Cambridge, MA, 02138, USA.ORCID http://orcid.org/0000-0002-8699-2404
Ilya LeventalDepartment of Molecular Physiology and Biological Physics, Center for Membrane and Cell Physiology, University of Virginia, Charlottesville, VA, 22903, USA.ORCID http://orcid.org/0000-0002-1206-9545
Natalie BoehnkeDepartment of Chemical Engineering and Materials Science, University of Minnesota, Minneapolis, MN, 55455, USA.
Victor W HsuDivision of Rheumatology, Inflammation and Immunity, Brigham and Women's Hospital, and Dept. of Medicine, Harvard Medical School, Boston, MA, 02115, USA.ORCID http://orcid.org/0000-0002-6763-4636
Kandice R LeventalDepartment of Molecular Physiology and Biological Physics, Center for Membrane and Cell Physiology, University of Virginia, Charlottesville, VA, 22903, USA.ORCID http://orcid.org/0000-0002-2234-3683
Raphaël RodriguezInstitut Curie, CNRS, INSERM, PSL Research University, Equipe Labellisée Ligue Contre le Cancer, Paris, 75005, France. raphael.rodriguez@curie.fr.ORCID http://orcid.org/0000-0001-7668-446X
Robert A WeinbergDepartment of Biology, MIT, Cambridge, MA, 02139, USA. weinberg@wi.mit.edu.ORCID http://orcid.org/0000-0002-0895-3557
Whitney S HenryDepartment of Biology, MIT, Cambridge, MA, 02139, USA. wshenry@mit.edu.ORCID http://orcid.org/0000-0002-2059-3996

Funding

Medical Scientist Training ProgramT32GM144273 · NIGMS · HARVARD MEDICAL SCHOOL · PI David Shumway Jones, Jacqueline A. Lees · 2022 to 2026
$14.7M
Pre-doctoral Training in Fundamental Approaches to Biochemistry and Cell and Molecular BiologyT32GM136540 · NIGMS · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI Mary Gehring, Michael Laub · 2021 to 2026
$9.5M
Mechanisms and Physiology of COPI TransportR37GM058615 · NIGMS · BRIGHAM AND WOMEN'S HOSPITAL · PI HSU, VICTOR W · 2016 to 2025
$6.0M
The functional organization of mammalian membranes-Equipment SupplementR35GM134949 · NIGMS · UNIVERSITY OF VIRGINIA · PI Ilya Levental · 2020 to 2026
$3.8M
EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 European Research Council (H2020 Excellent Science - European Research Council) 647973Institut National Du Cancer (French National Cancer Institute) INCa_16712Institut National Du Cancer (French National Cancer Institute) INCa 2022-1-PL BIO-05-ICR-1National Cancer Center K99CA255844National Cancer Center R00CA255844NIGMS NIH HHS T32 GM144273U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS) 1R21CA300756U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS) R35GM134949U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS) R37GM058615U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS) T32GM136540
6 · The paper itself

Abstract

Cancer cell fate has been widely ascribed to mutational changes within protein-coding genes associated with tumor suppressors and oncogenes. In contrast, the mechanisms through which the biophysical properties of membrane lipids influence cancer cell survival, dedifferentiation and metastasis have received little scrutiny. Here, we report that cancer cells endowed with high metastatic ability and cancer stem cell-like traits employ ether lipids to maintain low membrane tension and high membrane fluidity. Using genetic approaches and lipid reconstitution assays, we show that these ether lipid-regulated biophysical properties permit non-clathrin-mediated iron endocytosis via CD44, resulting in significant increases in intracellular redox-active iron and enhanced ferroptosis susceptibility. Using a combination of in vitro three-dimensional microvascular network systems and in vivo animal models, we show that loss of ether lipids from plasma membranes also strongly attenuates extravasation, metastatic burden and cancer stemness. These findings illuminate a mechanism whereby ether lipids in carcinoma cells serve as key regulators of malignant progression while conferring a unique vulnerability that can be exploited for therapeutic intervention.

Indexed as

IronMembrane LipidsNeoplasmsAnimalsCell Line, TumorCell MembraneEndocytosisFerroptosisHumansHyaluronan ReceptorsMiceNeoplastic Stem CellsHyaluronan ReceptorsIronMembrane Lipids

Identifiers

PMID41593071
PMCPMC12920898

What Socratic 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 Socratic graph.