RDF/XMLNTriplesTurtleShow queryShare
SubjectPredicateObject
http://purl.uniprot.org/citations/36476868http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/36476868http://www.w3.org/2000/01/rdf-schema#comment"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."xsd:string
http://purl.uniprot.org/citations/36476868http://purl.org/dc/terms/identifier"doi:10.1016/j.celrep.2022.111756"xsd:string
http://purl.uniprot.org/citations/36476868http://purl.uniprot.org/core/author"Dai T."xsd:string
http://purl.uniprot.org/citations/36476868http://purl.uniprot.org/core/author"Liu S."xsd:string
http://purl.uniprot.org/citations/36476868http://purl.uniprot.org/core/author"Wang H."xsd:string
http://purl.uniprot.org/citations/36476868http://purl.uniprot.org/core/author"Zhu B."xsd:string
http://purl.uniprot.org/citations/36476868http://purl.uniprot.org/core/author"Dasgupta S."xsd:string
http://purl.uniprot.org/citations/36476868http://purl.uniprot.org/core/author"Bshara W."xsd:string
http://purl.uniprot.org/citations/36476868http://purl.uniprot.org/core/author"Seshadri M."xsd:string
http://purl.uniprot.org/citations/36476868http://purl.uniprot.org/core/author"Abrams S.I."xsd:string
http://purl.uniprot.org/citations/36476868http://purl.uniprot.org/core/author"Katsuta E."xsd:string
http://purl.uniprot.org/citations/36476868http://purl.uniprot.org/core/author"Cortes Gomez E."xsd:string
http://purl.uniprot.org/citations/36476868http://purl.uniprot.org/core/author"Rosario S.R."xsd:string
http://purl.uniprot.org/citations/36476868http://purl.uniprot.org/core/author"Sawant Dessai A."xsd:string
http://purl.uniprot.org/citations/36476868http://purl.uniprot.org/core/author"Novickis A.T."xsd:string
http://purl.uniprot.org/citations/36476868http://purl.uniprot.org/core/author"Paterson E.J."xsd:string
http://purl.uniprot.org/citations/36476868http://purl.uniprot.org/core/date"2022"xsd:gYear
http://purl.uniprot.org/citations/36476868http://purl.uniprot.org/core/name"Cell Rep"xsd:string
http://purl.uniprot.org/citations/36476868http://purl.uniprot.org/core/pages"111756"xsd:string
http://purl.uniprot.org/citations/36476868http://purl.uniprot.org/core/title"Hypoxic activation of PFKFB4 in breast tumor microenvironment shapes metabolic and cellular plasticity to accentuate metastatic competence."xsd:string
http://purl.uniprot.org/citations/36476868http://purl.uniprot.org/core/volume"41"xsd:string
http://purl.uniprot.org/citations/36476868http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/36476868
http://purl.uniprot.org/citations/36476868http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/36476868
http://purl.uniprot.org/uniprot/#_C9VZF1-mappedCitation-36476868http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/36476868