ArticleCell reports2019
Inhibition of ERRα Prevents Mitochondrial Pyruvate Uptake Exposing NADPH-Generating Pathways as Targetable Vulnerabilities in Breast Cancer.
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 38 papers.
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Who cites it
38 citing papers in PubMed, 51 citations in OpenAlex.
- Tumor-Derived Exosomal circAP2B1 Induces M2 Macrophage Polarization by Enhancing Mitochondrial Homeostasis to Promote Esophageal Squamous Cell Carcinoma Progression.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Metabolic activation of LDHA by ERRα represses inflammasome-dependent pyroptosis and promotes ovarian cancer chemoresistance.Cell death & disease · 2026Article
- Long non-coding RNA LINC01532 sustains redox homeostasis and accelerates lenvatinib resistance in hepatocellular carcinoma.Journal of advanced research · 2025Article
- ERRα and HIF-1α Cooperate to Enhance Breast Cancer Aggressiveness and Chemoresistance Under Hypoxic Conditions.Cancers · 2025Article
- Advancing mitochondrial therapeutics: Synthesis and pharmacological evaluation of pyrazole-based inhibitors targeting the mitochondrial pyruvate carrier.European journal of medicinal chemistry · 2025Article
- Mitochondrial pyruvate dehydrogenase phosphatase metabolism disorder in malignant tumors.Oncology research · 2025Review
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- MARCH5 promotes aerobic glycolysis to facilitate ovarian cancer progression via ubiquitinating MPC1.Apoptosis : an international journal on programmed cell death · 2024Article
- Shikonin blocks CAF-induced TNBC metastasis by suppressing mitochondrial biogenesis through GSK-3β/NEDD4-1 mediated phosphorylation-dependent degradation of PGC-1α.Journal of experimental & clinical cancer research : CR · 2024Article
- GLS and GLS2 Glutaminase Isoenzymes in the Antioxidant System of Cancer Cells.Antioxidants (Basel, Switzerland) · 2024Review
- Estrogen-Related Receptor α: A Key Transcription Factor in the Regulation of Energy Metabolism at an Organismic Level and a Target of the ABA/LANCL Hormone Receptor System.International journal of molecular sciences · 2024Review
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- Oncogenic metabolic reprogramming in breast cancer: focus on signaling pathways and mitochondrial genes.Medical oncology (Northwood, London, England) · 2023Review
- Transcriptional control of energy metabolism by nuclear receptors.Nature reviews. Molecular cell biology · 2022Review
- Non-genetic stratification reveals epigenetic heterogeneity and identifies vulnerabilities of glycolysis addiction in lung adenocarcinoma subtype.Oncogenesis · 2022Article
- Estrogen Related Receptor Alpha (ERRα) a Bridge between Metabolism and Adrenocortical Cancer Progression.Cancers · 2022Article
- The mitochondrial pyruvate carrier at the crossroads of intermediary metabolism.American journal of physiology. Endocrinology and metabolism · 2022Review
- Role of HIF-1α/ERRα in Enhancing Cancer Cell Metabolism and Promoting Resistance of Endometrial Cancer Cells to Pyroptosis.Frontiers in oncology · 2022Review
- Emerging Roles of COX7RP and Mitochondrial Oxidative Phosphorylation in Breast Cancer.Frontiers in cell and developmental biology · 2022Review
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Most cancer cells exhibit metabolic flexibility, enabling them to withstand fluctuations in intratumoral concentrations of glucose (and other nutrients) and changes in oxygen availability. While these adaptive responses make it difficult to achieve clinically useful anti-tumor responses when targeting a single metabolic pathway, they can also serve as targetable metabolic vulnerabilities that can be therapeutically exploited. Previously, we demonstrated that inhibition of estrogen-related receptor alpha (ERRα) significantly disrupts mitochondrial metabolism and that this results in substantial antitumor activity in animal models of breast cancer. Here we show that ERRα inhibition interferes with pyruvate entry into mitochondria by inhibiting the expression of mitochondrial pyruvate carrier 1 (MPC1). This results in a dramatic increase in the reliance of cells on glutamine oxidation and the pentose phosphate pathway to maintain nicotinamide adenine dinucleotide phosphate (NADPH) homeostasis. In this manner, ERRα inhibition increases the efficacy of glutaminase and glucose-6-phosphate dehydrogenase inhibitors, a finding that has clinical significance.
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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.