Evidence map›Paper›PMID 38562716›Full record

ArticlebioRxiv : the preprint server for biology2025

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

Open access · greenAbstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

0 citing papers in PubMed, 8 citations in OpenAlex.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

31 authors at 11 institutions in 3 countries.

Ryan P MansellDept. of Biology, MIT, Cambridge, MA 02139, USA.ORCID 0000-0002-4480-3513
Sebastian MüllerInstitut Curie, CNRS, INSERM, PSL Research University, Equipe Labellisée Ligue Contre le Cancer, Paris 75005, France.
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-GoldDept. of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA.
Sunny DasWhitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.ORCID 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 PhadnisDept. of Biology, MIT, Cambridge, MA 02139, USA.
Zhengpeng WanDept. of Biological Engineering, MIT, Cambridge, MA 02139, USA.
Jillian StarkDept. of Biology, MIT, Cambridge, MA 02139, USA.ORCID 0009-0006-7924-1692
Daehee HwangDept. of Biology, MIT, Cambridge, MA 02139, USA.ORCID 0000-0003-1038-9200
Fabien SindikubwaboInstitut Curie, CNRS, INSERM, PSL Research University, Equipe Labellisée Ligue Contre le Cancer, Paris 75005, France.
Laurène SyxInstitut Curie, INSERM, Mines ParisTech, Paris 75005, France.
Nicolas ServantInstitut Curie, INSERM, Mines ParisTech, Paris 75005, France.
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.
Prathapan ThiruWhitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.
Amartya ViravalliDept. 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.
Clary B ClishThe Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.ORCID 0000-0001-8259-9245
Paula T HammondKoch Institute for Integrative Cancer Research, MIT, Cambridge, MA 02139, USA.
Roger D KammDept. of Biological Engineering, MIT, Cambridge, MA 02139, USA.
Adam E CohenDept. of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA.
Ilya LeventalDept. of Molecular Physiology and Biological Physics, Center for Membrane and Cell Physiology, University of Virginia, Charlottesville, VA 22903, USA.ORCID 0000-0002-1206-9545
Natalie BoehnkeDept. 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.
Kandice R LeventalDept. of Molecular Physiology and Biological Physics, Center for Membrane and Cell Physiology, University of Virginia, Charlottesville, VA 22903, USA.
Raphaël RodriguezInstitut Curie, CNRS, INSERM, PSL Research University, Equipe Labellisée Ligue Contre le Cancer, Paris 75005, France.
Robert A WeinbergDept. of Biology, MIT, Cambridge, MA 02139, USA.
Whitney S HenryDept. of Biology, MIT, Cambridge, MA 02139, USA.ORCID 0000-0002-2059-3996
IIT@MIT · USUniversity of Minnesota · USBrigham and Women's Hospital · USCentre National de la Recherche Scientifique · FRHarvard University · USWhitehead Institute for Biomedical Research · USBroad Institute · USInserm · FRUniversity of Virginia · USHoward Hughes Medical Institute · USLudwig Cancer Research · BE

Funding

VIRUS PRODUCTION COREP30CA014051 · NCI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI Jacqueline A. Lees · 1985 to 2026
$93.9M
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
Understanding drug delivery through an integrated barcoding approachR00CA255844 · NCI · UNIVERSITY OF MINNESOTA · PI BOEHNKE, NATALIE · 2022 to 2024
$584k
Tools for probing the physical paralipidome of membrane proteinsR21CA300756 · NCI · UNIVERSITY OF VIRGINIA · PI Kandice Rose Levental · 2025 to 2026
$410k
Understanding drug delivery through an integrated barcoding approachK99CA255844 · NCI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI BOEHNKE, NATALIE · 2021 to 2022
$308k
NCI NIH HHS K99 CA255844NCI NIH HHS P30 CA014051NCI NIH HHS R00 CA255844NCI NIH HHS R21 CA300756NIGMS NIH HHS R35 GM134949NIGMS NIH HHS R37 GM058615NIGMS NIH HHS T32 GM136540
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

CD44endocytosisEther lipidsferroptosisironmembrane tensionmetastasis

Identifiers

PMID38562716
PMCPMC10983928
OpenAlexW4393034843

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.