ArticleCell reports2022
Hypoxic activation of PFKFB4 in breast tumor microenvironment shapes metabolic and cellular plasticity to accentuate metastatic competence.
Article in Cell reports, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 24 citations in OpenAlex.
- WDR12 Promotes Glucose Metabolism via PFKFB4 Upregulation in Gastric Cancer.Cancer science · 2026Article
- Metabolic Vulnerabilities as a Therapeutic Target in Breast Cancer.Current oncology (Toronto, Ont.) · 2026Review
- Targeting one-carbon metabolic vulnerabilities of metastasis with therapeutic potential.bioRxiv : the preprint server for biology · 2026Article
- Targeting phosphofructokinase in cancer: integrating natural products for metabolic reprogramming and therapeutic innovation.Frontiers in pharmacology · 2026Review
- Integrated transcriptomic and microbiota analyses reveal growth-related intestinal responses to feeding strategies in Nibea coibor.Advanced biotechnology · 2025Article
- Targeting phosphofructokinase 2 the isoform PFKFB4 suppresses glioblastoma proliferation and malignancy.Genes & genomics · 2025Article
- A novel protein cPFKFB4 encoded by hsa_circ_0065394 strengthens PKM2-mediated glucose metabolic reprogramming to facilitate pancreatic cancer progression under hypoxia.Molecular cancer · 2025Article
- USP5 motivates immunosuppressive microenvironment in multiple myeloma by activating STAT2-PFKFB4-mediated glycolysis.Cancer immunology, immunotherapy : CII · 2025Article
- Identification and validation of a lenvatinib resistance-related prognostic signature in HCC, in which PFKFB4 contributes to tumor progression and lenvatinib resistance.BMC gastroenterology · 2025Article
- Comprehensive Analysis Reveals the Potential Diagnostic Value of Biomarkers Associated With Aging and Circadian Rhythm in Knee Osteoarthritis.Orthopaedic surgery · 2025Article
- Single-Cell RNA-Seq Analysis Links DNMT3B and PFKFB4 Transcriptional Profiles with Metastatic Traits in Hepatoblastoma.Biomolecules · 2024Article
- Metabolic Signaling in Cancer Metastasis.Cancer discovery · 2024Review
- The Molecular Mechanisms behind Advanced Breast Cancer Metabolism: Warburg Effect, OXPHOS, and Calcium.Frontiers in bioscience (Landmark edition) · 2024Review
- Mini review of photoacoustic clinical imaging: a noninvasive tool for disease diagnosis and treatment evaluation.Journal of biomedical optics · 2024Review
- Review
- Rewiring of mitochondrial metabolism in therapy-resistant cancers: permanent and plastic adaptations.Frontiers in cell and developmental biology · 2023Review
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Authors and funding
14 authors at 2 institutions in 1 country.
Funding
Abstract
Cancer cells encounter a hostile tumor microenvironment (TME), and their adaptations to metabolic stresses determine metastatic competence. Here, we show that the metabolic enzyme 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase-4 (PFKFB4) is induced in hypoxic tumors acquiring metabolic plasticity and invasive phenotype. In mouse models of breast cancer, genetic ablation of PFKFB4 significantly delays distant organ metastasis, reducing local lymph node invasion by suppressing expression of invasive gene signature including integrin β3. Photoacoustic imaging followed by metabolomics analyses of hypoxic tumors show that PFKFB4 drives metabolic flexibility, enabling rapid detoxification of reactive oxygen species favoring survival under selective pressure. Mechanistically, hypoxic induction triggers nuclear translocation of PFKFB4 accentuating non-canonical transcriptional activation of HIF-1α, and breast cancer patients with increased nuclear PFKFB4 in their tumors are found to be significantly associated with poor prognosis. Our findings imply that PFKFB4 induction is crucial for tumor cell adaptation in the hypoxic TME that determines metastatic competence.
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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.