Evidence map›Paper›PMID 41997112›Full record

ArticleMolecular cell2026

mTORC1 activity suppresses ferroptosis through a SCARB1-dependent HDL-tocopherol uptake pathway.

Thomas A O'Loughlin, John S Stiles, Pritika Acharya, Abolfazl Arab, Laine Goudy, Raymond Dai, Ashir A Borah, William A Weiss, Uche N Medoh, Luke A Gilbert

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular cell, 2026. 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.

No citing paper in PubMed yet.

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

10 authors.

Thomas A O'LoughlinNash Family Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Marie-Josee and Henry R. Kravis Drug Discovery Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Urology, University of California, San Francisco, San Francisco, CA 94158, USA; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94158, USA. Electronic address: thomas.oloughlin@mssm.edu.
John S StilesArc Institute, Palo Alto, CA 94304, USA.
Pritika AcharyaNash Family Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Marie-Josee and Henry R. Kravis Drug Discovery Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Abolfazl ArabDepartment of Urology, University of California, San Francisco, San Francisco, CA 94158, USA; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94158, USA; Arc Institute, Palo Alto, CA 94304, USA; Graduate Program in Pharmaceutical Sciences and Pharmacogenomics, University of California, San Francisco, San Francisco, CA 94158, USA.
Laine GoudyDepartment of Urology, University of California, San Francisco, San Francisco, CA 94158, USA; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94158, USA; Arc Institute, Palo Alto, CA 94304, USA; Biomedical Sciences Graduate Program, University of California, San Francisco, San Francisco, CA 94158, USA; Gladstone-UCSF Institute of Genomic Immunology, San Francisco, CA 94158, USA.
Raymond DaiDepartment of Urology, University of California, San Francisco, San Francisco, CA 94158, USA; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94158, USA; Arc Institute, Palo Alto, CA 94304, USA; Biomedical Sciences Graduate Program, University of California, San Francisco, San Francisco, CA 94158, USA.
Ashir A BorahArc Institute, Palo Alto, CA 94304, USA.
William A WeissHelen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94158, USA; Department of Neurology, University of California, San Francisco, San Francisco, CA 94158, USA; Department of Pediatrics, University of California, San Francisco, San Francisco, CA 94158, USA; Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA 94158, USA.
Uche N MedohArc Institute, Palo Alto, CA 94304, USA.
Luke A GilbertDepartment of Urology, University of California, San Francisco, San Francisco, CA 94158, USA; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94158, USA; Arc Institute, Palo Alto, CA 94304, USA. Electronic address: luke@arcinstitute.org.

Funding

A GENETIC INTERACTION MAP OF THE HUMAN NUCLEUSDP2CA239597 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI GILBERT, LUKE · 2018 to 2018
$2.4M
NCI NIH HHS DP2 CA239597
6 · The paper itself

Abstract

Aberrant activation of the PI3K/AKT/mTOR signaling pathway is a common feature of cancer, but while mTOR kinase represents an attractive drug target, mTOR inhibitors have not seen broad success as single agents. To identify strategies to enhance the utility of third-generation bi-steric mTORC1 inhibitors, we performed genome-scale CRISPR interference chemogenomics screens, which revealed that mTORC1 inhibitor-mediated cytostasis leaves cells exquisitely dependent on the lipid peroxide scavenging enzyme GPX4. Mechanistically, using unbiased CRISPR activation chemogenomics screens, we demonstrate that mTORC1-dependent control of ferroptosis occurs, in part, through regulation of SCARB1 expression. Specifically, we find that the high-density lipoprotein (HDL) can suppress ferroptosis through interaction with its receptor SCARB1 and delivery of vitamin E to target cells. Our work highlights combining mTORC1 with GPX4 inhibition as one of the most promising combinatorial approaches for mTOR-targeted cancer therapies and defines an HDL-SCARB1 ferroptosis-suppression system that is regulated by mTORC1 activity.

Indexed as

FerroptosisLipoproteins, HDLMechanistic Target of Rapamycin Complex 1Scavenger Receptors, Class BAnimalsCell Line, TumorHEK293 CellsHumansPhospholipid Hydroperoxide Glutathione PeroxidaseSignal TransductionVitamin ELipoproteins, HDLMechanistic Target of Rapamycin Complex 1Phospholipid Hydroperoxide Glutathione PeroxidaseSCARB1 protein, humanScavenger Receptors, Class BVitamin Eantioxidantcancercell biologyferroptosisfunctional genomicsGPX4HDLlipoproteinmTORSCARB1tocopherolvitamin E

Identifiers

PMID41997112
PMCPMC13404514

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.