Evidence map›Paper›PMID 35882862›Full record

ArticleNature communications2022

Targeting de novo lipogenesis and the Lands cycle induces ferroptosis in KRAS-mutant lung cancer.

Caterina Bartolacci, Cristina Andreani, Gonçalo Vale, Stefano Berto, Margherita Melegari, Anna Colleen Crouch, Dodge L Baluya, George Kemble, Kurt Hodges, Jacqueline Starrett and 12 more

Erratum issuedOpen access · goldAbstract read
In one paragraph

Article in Nature communications, 2022. 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 126 papers.

0numbers the graph read from it
0cells of the map it votes in
126citing papers in PubMed
14.0field-weighted citation impact, top 1% 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

126 citing papers in PubMed, 161 citations in OpenAlex.

  1. Phase II Investigation of TVB-2640 (Denifanstat) with Bevacizumab in Patients with First Relapse High-Grade Astrocytoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023
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  20. ProteinbioRxiv : the preprint server for biology · 2026
    Article

66 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

22 authors at 7 institutions in 2 countries.

Caterina Bartolacci *Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, OH, 45219, USA.
Cristina Andreani *Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, OH, 45219, USA.ORCID 0000-0003-3245-670X
Gonçalo ValeCenter for Human Nutrition, The University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA.ORCID 0000-0003-1104-0289
Stefano BertoDepartment of Neuroscience, The University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA.ORCID 0000-0001-9028-9458
Margherita MelegariDepartment of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, OH, 45219, USA.
Anna Colleen CrouchDepartment of Interventional Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Dodge L BaluyaTissue Imaging and Proteomics Laboratory, Washington State University, Pullman, WA, 99164, USA.
George KembleSagimet Biosciences, San Mateo, CA, 94402, USA.
Kurt HodgesDepartment of Pathology, University of Cincinnati College of Medicine, Cincinnati, OH, 45219, USA.
Jacqueline StarrettYale Cancer Center, Yale School of Medicine, New Haven, CT, USA.
Katerina PolitiYale Cancer Center, Yale School of Medicine, New Haven, CT, USA.
Sandra L StarnesDepartment of Surgery, Division of Thoracic Surgery, University of Cincinnati College of Medicine, Cincinnati, OH, 45219, USA.
Daniele LorenziniDepartment of Pathology, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, via Venezian 1, 20133, Milan, Italy.
Maria Gabriela RasoDepartment of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.ORCID 0000-0003-2105-5556
Luisa M Solis SotoDepartment of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.ORCID 0000-0002-1253-630X
Carmen BehrensDepartment of Thoracic H&N Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Humam KadaraDepartment of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Boning GaoHamon Center for Therapeutic Oncology Research, The University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA.ORCID 0000-0002-1382-395X
Ignacio I WistubaDepartment of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
John D MinnaHamon Center for Therapeutic Oncology Research, The University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA.ORCID 0000-0002-7776-0767
Jeffrey G McDonaldCenter for Human Nutrition, The University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA.ORCID 0000-0003-1570-4142
Pier Paolo ScaglioniDepartment of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, OH, 45219, USA. Scaglipr@ucmail.uc.edu.ORCID 0000-0002-6036-5138
The University of Texas MD Anderson Cancer Center · USThe University of Texas Southwestern Medical Center · USUniversity of Cincinnati Medical Center · USYale Cancer Center · USFondazione IRCCS Istituto Nazionale dei Tumori · ITUniversity of Cincinnati · USWashington State University · US

Funding

Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Fabien Delerue · 1985 to 2026
$290.8M
TRANSCRIPTIONAL REGULATION OF LDL RECEPTOR PROMOTERP01HL020948 · NHLBI · UT SOUTHWESTERN MEDICAL CENTER · PI GOLDSTEIN, JOSEPH L · 1985 to 2021
$103.1M
UNIVERSITY OF TEXAS--SPORE IN LUNG CANCERP50CA070907 · NCI · UT SOUTHWESTERN MEDICAL CENTER · PI HEYMACH, JOHN V., MINNA, JOHN D. · 1996 to 2024
$57.4M
Yale SPORE in Lung Cancer (YSILC): The Biology and Personalized Treatment of Lung CancerP50CA196530 · NCI · YALE UNIVERSITY · PI Kurt A Schalper · 2015 to 2026
$31.1M
UT Southwestern NORCP30DK127984 · NIDDK · UT SOUTHWESTERN MEDICAL CENTER · PI Jeff G McDonald · 2022 to 2026
$7.4M
Fatty acid metabolism regulates ferroptosis in mutant KRAS lung cancerR01CA259845 · NCI · UNIVERSITY OF CINCINNATI · PI PIER Paolo SCAGLIONI · 2022 to 2026
$2.0M
NCI NIH HHS P30 CA016672NCI NIH HHS P50 CA070907NCI NIH HHS P50 CA196530NCI NIH HHS R01 CA259845NHLBI NIH HHS P01 HL020948NIDDK NIH HHS P30 DK127984
6 · The paper itself

Abstract

Mutant KRAS (KM), the most common oncogene in lung cancer (LC), regulates fatty acid (FA) metabolism. However, the role of FA in LC tumorigenesis is still not sufficiently characterized. Here, we show that KMLC has a specific lipid profile, with high triacylglycerides and phosphatidylcholines (PC). We demonstrate that FASN, the rate-limiting enzyme in FA synthesis, while being dispensable in EGFR-mutant or wild-type KRAS LC, is required for the viability of KMLC cells. Integrating lipidomic, transcriptomic and functional analyses, we demonstrate that FASN provides saturated and monounsaturated FA to the Lands cycle, the process remodeling oxidized phospholipids, such as PC. Accordingly, blocking either FASN or the Lands cycle in KMLC, promotes ferroptosis, a reactive oxygen species (ROS)- and iron-dependent cell death, characterized by the intracellular accumulation of oxidation-prone PC. Our work indicates that KM dictates a dependency on newly synthesized FA to escape ferroptosis, establishing a targetable vulnerability in KMLC.

Indexed as

FerroptosisLung NeoplasmsHumansLipid MetabolismLipogenesisPhosphatidylcholinesProto-Oncogene Proteins p21(ras)KRAS protein, humanPhosphatidylcholinesProto-Oncogene Proteins p21(ras)

Identifiers

PMID35882862
PMCPMC9325712
OpenAlexW4288068925

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Registered trials

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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.