ArticleProceedings of the National Academy of Sciences of the United States of America2019
Elucidating cancer metabolic plasticity by coupling gene regulation with metabolic pathways.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 223 papers, 2 of them syntheses that pooled it.
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Who cites it
223 citing papers in PubMed, 2 syntheses or guidelines pooled it, 342 citations in OpenAlex.
- Research progresses and hotspots on glucose metabolic reprogramming in breast cancer: a bibliometric analysis over the past two decades.Frontiers in oncology · 2024Pooled it
- PD-L1 Activity Is Associated with Partial EMT and Metabolic Reprogramming in Carcinomas.Current oncology (Toronto, Ont.) · 2022Pooled it
- Mitochondrial dynamics: A promising tool for personalized TNBC management.Genes & diseases · 2026Review
- A State-Gated Metallo-DNAzyme Framework Programs Tumor Stress Vulnerability Through Metabolic Licensing.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Age-Associated NAD+ Decline and Mitochondrial Dysfunction Predispose Cells to a Reversible Tumor-Permissive Metabolic State.Biology · 2026Article
- KRAS Signaling Inhibition Induces a Targetable Metabolic Dependency on Lipophagy-Dependent Fatty Acid Oxidation in Pancreatic Cancer.Cancer research · 2026Article
- Metab8D: a metabolic regulome network from multiomics and machine learning.Communications biology · 2026Article
- Adrenal-derived factors drive progression of sclerotic prostate cancer in bone.Endocrine-related cancer · 2026Article
- Combating VEGFA-siRNA-Induced Metabolic Reprogramming via Glucose Utilization Deprivation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- BMX-001 acts as a selective chemoradioprotector in rectal cancer.Redox biochemistry and chemistry · 2026Article
- Cellular mechanometabolism: stimuli and implications.EMBO reports · 2026Review
- Hallmarks of epithelial-mesenchymal plasticity in cancer.Molecular cancer · 2026Review
- Article
- Review
- Absolute dynamic and relative static: the relationship of glycolysis and OXPHOS in cancer development.Cell death discovery · 2026Review
- ROS-Fueled Allies: STAT3, PKM2, and HIF-1α Influencing Energy Metabolism in Hormone-Independent Cancers.International journal of molecular sciences · 2026Article
- Single-Cell Transcriptomic Landscape of Right-Sided Colon Cancer Reveals Cellular and Molecular Features of Metastatic Potential.Biomedicines · 2026Article
- Fraternal cooperation of hierarchical cancer parallels metazoan multicellularity and eusociality.Biological reviews of the Cambridge Philosophical Society · 2026Review
- Methionine metabolism and the NOP2 methyltransferase are essential for MYC-Driven liver tumorigenesis.bioRxiv : the preprint server for biology · 2026Article
- Defining the cellular and molecular identities of histologic subtypes in lung adenocarcinoma.Experimental hematology & oncology · 2026Article
163 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Metabolic plasticity enables cancer cells to switch their metabolism phenotypes between glycolysis and oxidative phosphorylation (OXPHOS) during tumorigenesis and metastasis. However, it is still largely unknown how cancer cells orchestrate gene regulation to balance their glycolysis and OXPHOS activities. Previously, by modeling the gene regulation of cancer metabolism we have reported that cancer cells can acquire a stable hybrid metabolic state in which both glycolysis and OXPHOS can be used. Here, to comprehensively characterize cancer metabolic activity, we establish a theoretical framework by coupling gene regulation with metabolic pathways. Our modeling results demonstrate a direct association between the activities of AMPK and HIF-1, master regulators of OXPHOS and glycolysis, respectively, with the activities of three major metabolic pathways: glucose oxidation, glycolysis, and fatty acid oxidation. Our model further characterizes the hybrid metabolic state and a metabolically inactive state where cells have low activity of both glycolysis and OXPHOS. We verify the model prediction using metabolomics and transcriptomics data from paired tumor and adjacent benign tissue samples from a cohort of breast cancer patients and RNA-sequencing data from The Cancer Genome Atlas. We further validate the model prediction by in vitro studies of aggressive triple-negative breast cancer (TNBC) cells. The experimental results confirm that TNBC cells can maintain a hybrid metabolic phenotype and targeting both glycolysis and OXPHOS is necessary to eliminate their metabolic plasticity. In summary, our work serves as a platform to symmetrically study how tuning gene activity modulates metabolic pathway activity, and vice versa.
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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.