ArticleCell reports2019
Metabolic Rewiring in Response to Biguanides Is Mediated by mROS/HIF-1a in Malignant Lymphocytes.
Article in Cell reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 1 of them a synthesis that pooled it.
What it found
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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.
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Who cites it
28 citing papers in PubMed, 1 synthesis or guideline pooled it, 40 citations in OpenAlex.
- Multilevel Mechanisms of Cancer Drug Resistance.International journal of molecular sciences · 2024Pooled it
- Glucose-induced histone lactylation confers metformin resistance in colorectal cancer stem cells.Nature communications · 2026Article
- Mitochondrial superoxide sustains a senescence-like phenotype in PARP- inhibited ovarian cancer cells by stabilizing HIF1α.Redox biology · 2026Article
- The pyruvate branch point controls lymphoid cancer cell dissemination.bioRxiv : the preprint server for biology · 2026Article
- Cuproptosis-associated PDHA1 promotes sarcoma progression and immunotherapy responsiveness via the E2F1-PD-L1 axis: a multi-omics and clinical validation study.NPJ precision oncology · 2026Article
- Single-cell sequencing reveals PHLDA1-positive smooth muscle cells promote local invasion in head and neck squamous cell carcinoma.Translational oncology · 2025Article
- Spring viremia of carp virus infection induces hypoxia response in zebrafish by stabilizing hif1α.Journal of virology · 2025Article
- Progress in antitumor mechanisms and applications of phenformin (Review).Oncology reports · 2024Review
- Oxygen enhances antiviral innate immunity through maintenance of EGLN1-catalyzed proline hydroxylation of IRF3.Nature communications · 2024Article
- HIF-1 regulates pathogenic cytotoxic T cells in lupus skin disease.JCI insight · 2023Article
- Cholesterol suppresses human iTreg differentiation and nTreg function through mitochondria-related mechanisms.Journal of translational medicine · 2023Article
- Selective cytotoxicity of a novel mitochondrial complex I inhibitor, YK-135, against EMT-subtype gastric cancer cell lines due to impaired glycolytic capacity.BMB reports · 2022Article
- Melatonin inhibits NaIOCell & bioscience · 2022Article
- Review
- Rewired Cellular Metabolic Profiles in Response to Metformin under Different Oxygen and Nutrient Conditions.International journal of molecular sciences · 2022Article
- miR-138-5p Inhibits Vascular Mimicry by Targeting the HIF-1Journal of immunology research · 2022Article
- Trophoblast-derived Lactic Acid Orchestrates Decidual Macrophage Differentiation via SRC/LDHA Signaling in Early Pregnancy.International journal of biological sciences · 2022Article
- Therapeutic Repurposing of Biguanides in Cancer.Trends in cancer · 2021Review
- Oncogenic Mechanisms and Therapeutic Targeting of Metabolism in Leukemia and Lymphoma.Cold Spring Harbor perspectives in medicine · 2021Review
- Development of antitumor biguanides targeting energy metabolism and stress responses in the tumor microenvironment.Scientific reports · 2021Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
Abstract
Metabolic flexibility allows cells to adapt to various environments and limits the efficacy of metabolic drugs. Therapeutic targeting of cancer metabolism relies on defining limiting requirements and vulnerabilities in the highly dynamic metabolic network. Here, we characterize the metabolic reprogramming and identify cancer-specific metabolic vulnerabilities in response to the pharmacological inhibition of mitochondrial complex I. Our work reveals the adaptation mechanism in malignant lymphocytes providing resistance against the biguanides phenformin and metformin by transcriptionally reprogramming glucose metabolism. Metabolic adaptation to complex I inhibition is mediated by mitochondrial reactive oxygen species (mROS) serving as a mitochondrial stress signal activating hypoxia-inducible factor-1a (HIF-1a). Inhibition of the mROS/HIF-1a axis through antioxidants or direct suppression of HIF-1a selectively disrupts metabolic adaptation and survival during complex I dysfunction in malignant lymphocytes. Our results identify HIF-1a signaling as a critical factor in resistance against biguanide-induced mitochondrial dysfunction, allowing selective targeting of metabolic pathways in leukemia and lymphoma.
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Registered trials
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.