ArticleOpen biology2016
Notch stimulates growth by direct regulation of genes involved in the control of glycolysis and the tricarboxylic acid cycle.
Article in Open biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers, 1 of them a synthesis that pooled it.
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Who cites it
50 citing papers in PubMed, 1 synthesis or guideline pooled it, 74 citations in OpenAlex.
- Functional Gene Expression Differentiation of the Notch Signaling Pathway in Female Reproductive Tract Tissues-A Comprehensive Review With Analysis.Frontiers in cell and developmental biology · 2020Pooled it
- Development and preclinical evaluation of a decoy DLL4-encoding oncolytic HSV-1 for high-grade glioma.Oncogene · 2026Article
- Live imaging and multimodal profiling reveal transdifferentiation of a cochlear supporting cell subpopulation upon Notch inhibition.Science advances · 2026Article
- Lactate metabolism and lactylation in cancer: from pathogenesis to therapeutic advances.Signal transduction and targeted therapy · 2026Review
- Remodeling of Metabolic and Secretory Organelles During Oncogenic and Oncomodulatory Viral Infections.Viruses · 2026Review
- Explore the Heterogeneity of Glioblastoma Based on Genes Related to Glutamine Metabolism.Cancer informatics · 2026Article
- Treatment with mitochondrial targeting antibiotics improves survival outcomes after Flock House virus infection in young and aged Drosophila melanogaster.Research square · 2025Article
- From laboratory to clinic: opportunities and challenges of functional food active ingredients in cancer therapy.Frontiers in nutrition · 2025Review
- [GINS1 Enhances Glycolysis, Proliferation and Metastasis in Lung Adenocarcinoma Cells by Activating the Notch/PI3K/AKT/mTORC1 Signaling Pathway].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2024Article
- Metabolomics analyses reveal the crucial role of ERK in regulating metabolic pathways associated with the proliferation of human cutaneous T-cell lymphoma cells treated with Glabridin.Cell proliferation · 2024Article
- Dichloroacetate for Cancer Treatment: Some Facts and Many Doubts.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Notch signaling pathway in cancer: from mechanistic insights to targeted therapies.Signal transduction and targeted therapy · 2024Review
- Retinoic Acid-Mediated Control of Energy Metabolism Is Essential for Lung Branching Morphogenesis.International journal of molecular sciences · 2024Article
- Novel Genome-EngineeredGenes · 2024Article
- Reprogramming of glucose metabolism: Metabolic alterations in the progression of osteosarcoma.Journal of bone oncology · 2024Review
- Notch signaling regulates a metabolic switch through inhibiting PGC-1α and mitochondrial biogenesis in dedifferentiated liposarcoma.Oncogene · 2023Article
- Notch mediates the glycolytic switch via PI3K/Akt signaling to support embryonic development.Cellular & molecular biology letters · 2023Article
- Genetic and Molecular Interactions betweenGenes · 2023Article
- Immunometabolic regulation during the presence of microorganisms and parasitoids in insects.Frontiers in immunology · 2023Review
- Hedgehog signaling can enhance glycolytic ATP production in the Drosophila wing disc.EMBO reports · 2022Article
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
Abstract
Glycolytic shift is a characteristic feature of rapidly proliferating cells, such as cells during development and during immune response or cancer cells, as well as of stem cells. It results in increased glycolysis uncoupled from mitochondrial respiration, also known as the Warburg effect. Notch signalling is active in contexts where cells undergo glycolytic shift. We decided to test whether metabolic genes are direct transcriptional targets of Notch signalling and whether upregulation of metabolic genes can help Notch to induce tissue growth under physiological conditions and in conditions of Notch-induced hyperplasia. We show that genes mediating cellular metabolic changes towards the Warburg effect are direct transcriptional targets of Notch signalling. They include genes encoding proteins involved in glucose uptake, glycolysis, lactate to pyruvate conversion and repression of the tricarboxylic acid cycle. The direct transcriptional upregulation of metabolic genes is PI3K/Akt independent and occurs not only in cells with overactivated Notch but also in cells with endogenous levels of Notch signalling and in vivo. Even a short pulse of Notch activity is able to elicit long-lasting metabolic changes resembling the Warburg effect. Loss of Notch signalling in Drosophila wing discs as well as in human microvascular cells leads to downregulation of glycolytic genes. Notch-driven tissue overgrowth can be rescued by downregulation of genes for glucose metabolism. Notch activity is able to support growth of wing during nutrient-deprivation conditions, independent of the growth of the rest of the body. Notch is active in situations that involve metabolic reprogramming, and the direct regulation of metabolic genes may be a common mechanism that helps Notch to exert its effects in target tissues.
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