ArticleCell metabolism2023
NRF2 activation induces NADH-reductive stress, providing a metabolic vulnerability in lung cancer.
Erratum issuedOpen access · greenAbstract read
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Article in Cell metabolism, 2023. 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 84 papers.
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84 citing papers in PubMed, 127 citations in OpenAlex.
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- Recent advances in engineered nanozymes for precision lung cancer therapy.Materials today. Bio · 2026Review
- Metformin-restricted motility of an NRF2-activated lung cancer cell line involves NAD+ depletion, rather than AMPK- or BACH1 signaling.Scientific reports · 2026Article
- Impact of mitochondrial reductive stress due to respiratory chain limitation on cancer via posttranslational modifications.Redox biology · 2026Review
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- Role of oxidative stress in sepsis: Mechanisms, pathways, and therapeutic strategies.Journal of pharmaceutical analysis · 2026Review
- Excess cysteine drives conjugate formation and impairs proliferation of NRF2-activated cancer cells.Nature metabolism · 2026Article
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- Zearalenone Induces Oxidative Stress and Apoptosis in the Jejunum of Weaned Piglets via the p53/Nrf2 Signaling Pathway.International journal of molecular sciences · 2026Article
- Function and regulation of the mitochondrial stress response.Nature structural & molecular biology · 2026Review
- Insights into the mechanisms of drug resistance in renal cell carcinoma: from multi-omics perspective.International journal of surgery (London, England) · 2026Article
24 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
27 authors at 3 institutions in 1 country.
Tommy Weiss-SadanCenter for Cancer Research, Massachusetts General Hospital, Boston, MA 02114, USA.
Maolin GeCenter for Cancer Research, Massachusetts General Hospital, Boston, MA 02114, USA. Electronic address: mge1@mgh.harvard.edu.
Makiko HayashiDepartment of Pathology, New York University Grossman School of Medicine, 550 First Avenue, New York, NY 10016, USA; Laura and Isaac Pelmutter Cancer Center, New York University Langone Health, New York, NY 10016, USA.
Magdy GoharCenter for Cancer Research, Massachusetts General Hospital, Boston, MA 02114, USA.
Cong-Hui YaoDepartment of Cell Biology, Blavatnik Institute Harvard Medical School, Boston, MA 02115, USA.
Adriaan de GrootCenter for Cancer Research, Massachusetts General Hospital, Boston, MA 02114, USA.
Stefan HarryCenter for Cancer Research, Massachusetts General Hospital, Boston, MA 02114, USA.
Alexander CarlinCenter for Cancer Research, Massachusetts General Hospital, Boston, MA 02114, USA.
Hannah FischerCenter for Cancer Research, Massachusetts General Hospital, Boston, MA 02114, USA.
Lei ShiCenter for Cancer Research, Massachusetts General Hospital, Boston, MA 02114, USA.
Ting-Yu WeiCenter for Cancer Research, Massachusetts General Hospital, Boston, MA 02114, USA.
Charles H AdelmannCenter for Cancer Research, Massachusetts General Hospital, Boston, MA 02114, USA; Cutaneous Biology Research Center, Massachusetts General Hospital, Boston, MA 02114, USA.
Konstantin WolfCenter for Cancer Research, Massachusetts General Hospital, Boston, MA 02114, USA.
Tristan VornbäumenCenter for Cancer Research, Massachusetts General Hospital, Boston, MA 02114, USA.
Benedikt R DürrCenter for Cancer Research, Massachusetts General Hospital, Boston, MA 02114, USA.
Mariko TakahashiCenter for Cancer Research, Massachusetts General Hospital, Boston, MA 02114, USA.
Marianne RichterCenter for Cancer Research, Massachusetts General Hospital, Boston, MA 02114, USA.
Junbing ZhangCenter for Cancer Research, Massachusetts General Hospital, Boston, MA 02114, USA.
Tzu-Yi YangCenter for Cancer Research, Massachusetts General Hospital, Boston, MA 02114, USA.
Vindhya VijayCenter for Cancer Research, Massachusetts General Hospital, Boston, MA 02114, USA.
David E FisherCenter for Cancer Research, Massachusetts General Hospital, Boston, MA 02114, USA; Cutaneous Biology Research Center, Massachusetts General Hospital, Boston, MA 02114, USA.
Aaron N HataCenter for Cancer Research, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Medicine, Harvard Medical School, Boston, MA 02114, USA.
Marcia C HaigisDepartment of Cell Biology, Blavatnik Institute Harvard Medical School, Boston, MA 02115, USA.
Raul MostoslavskyCenter for Cancer Research, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Medicine, Harvard Medical School, Boston, MA 02114, USA.
Nabeel BardeesyCenter for Cancer Research, Massachusetts General Hospital, Boston, MA 02114, USA; The MGH Center for Regenerative Medicine, Harvard Medical School, Boston, MA 02114, USA.
Thales PapagiannakopoulosDepartment of Pathology, New York University Grossman School of Medicine, 550 First Avenue, New York, NY 10016, USA; Laura and Isaac Pelmutter Cancer Center, New York University Langone Health, New York, NY 10016, USA.
Liron Bar-PeledCenter for Cancer Research, Massachusetts General Hospital, Boston, MA 02114, USA; The MGH Center for Regenerative Medicine, Harvard Medical School, Boston, MA 02114, USA. Electronic address: lbar-peled@mgh.harvard.edu.
Massachusetts General Hospital · USHarvard University · USNYU Langone Health · US
Funding
Tissue and Pathology ResourcesP50CA127003 · NCI · DANA-FARBER CANCER INST · PI BASS, ADAM JOEL · 2007 to 2023
$33.2MTranscriptional mechanisms and melanomaP01CA163222 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI DAVID E FISHER · 2013 to 2026
$25.3MThe MITF transcriptional network: melanoma risk and carcinogenesisR01AR043369 · NIAMS · MASSACHUSETTS GENERAL HOSPITAL · PI DAVID E FISHER · 1996 to 2026
$9.4MTherapeutic strategies for treatment of giant congenital melanocytic neviR01AR072304 · NIAMS · MASSACHUSETTS GENERAL HOSPITAL · PI DAVID E FISHER · 2017 to 2026
$3.9MTargeting novel therapeutic vulnerabilities in LKB1 mutant tumors.R01CA219670 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI EL-BARDEESY, NABEEL, WONG, KWOK KIN · 2018 to 2022
$3.4MIdentifying metabolic dependencies in genetic subtypes of KRAS-driven lung cancerR37CA222504 · NCI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI PAPAGIANNAKOPOULOS, THALES · 2018 to 2024
$3.3MMechanistic Understanding for the Role of Lin28b in Pancreatic Cancer ProgressionR01CA235412 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI EL-BARDEESY, NABEEL, MOSTOSLAVSKY, RAUL · 2019 to 2023
$3.2MSirtuins and CancerR01CA273461 · NCI · HARVARD MEDICAL SCHOOL · PI MARCIA HAIGIS · 2022 to 2026
$2.9MFunctions of the LKB1 tumor suppressor in control in metabolism and epigenticsR01CA215498 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI EL-BARDEESY, NABEEL · 2018 to 2022
$2.7MProgenitor cell states contributing to aging and lung cancerU01CA267827 · NCI · HARVARD MEDICAL SCHOOL · PI HAIGIS, MARCIA, KIM, CARLA F. · 2021 to 2025
$2.2MUncovering Genotype Specific Vulnerabilities in KRAS Mutant Lung Cancer?R01CA227649 · NCI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI PAPAGIANNAKOPOULOS, THALES · 2018 to 2022
$1.9MDeciphering the Role of Reductive Stress in Non Small Cell Lung CancerR37CA260062 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI Liron Bar-Peled · 2022 to 2026
$1.9MNCI NIH HHS P01 CA163222NCI NIH HHS P50 CA127003NCI NIH HHS R00 CA215249NCI NIH HHS R01 CA215498NCI NIH HHS R01 CA219670NCI NIH HHS R01 CA222871NCI NIH HHS R01 CA227649NCI NIH HHS R01 CA235412NCI NIH HHS R01 CA273461NCI NIH HHS R21 CA256082NCI NIH HHS R37 CA222504NCI NIH HHS R37 CA260062NCI NIH HHS U01 CA267827NIAMS NIH HHS R01 AR043369NIAMS NIH HHS R01 AR072304NIGMS NIH HHS R01 GM128448
Abstract
Multiple cancers regulate oxidative stress by activating the transcription factor NRF2 through mutation of its negative regulator, KEAP1. NRF2 has been studied extensively in KEAP1-mutant cancers; however, the role of this pathway in cancers with wild-type KEAP1 remains poorly understood. To answer this question, we induced NRF2 via pharmacological inactivation of KEAP1 in a panel of 50+ non-small cell lung cancer cell lines. Unexpectedly, marked decreases in viability were observed in >13% of the cell lines-an effect that was rescued by NRF2 ablation. Genome-wide and targeted CRISPR screens revealed that NRF2 induces NADH-reductive stress, through the upregulation of the NAD
Indexed as
Carcinoma, Non-Small-Cell LungLung NeoplasmsNF-E2-Related Factor 2Cell Line, TumorHumansKelch-Like ECH-Associated Protein 1NADOxidative StressSignal TransductionKelch-Like ECH-Associated Protein 1NADNFE2L2 protein, humanNF-E2-Related Factor 2functional genomicNADH/NAD(+)non-small cell lung cancerNRF2-KEAP1 pathwayoxidative phosphorylationreductive stress
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