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PFKM promotes the survival of GBM cells under glucose deprivation

ABSTRACT: PFKM is the second rate-limiting step of glycolysis, catalyzing the phosphorylation of fructose 6-phosphate to fructose 1,6-bisphosphate. Here we show, using an orthotopic xenograft glioma mouse model, that PFKM is deubiquitinated and translocated into nucleus upon glucose deficiency, thereby activating fatty acid oxidation (FAO), which sustains tumor cell survival and ultimately promotes GBM development.

ORGANISM(S): Homo Sapiens

SUBMITTER: Weiwei Yang

PROVIDER: PXD074827 | iProX | Sun Feb 15 00:00:00 GMT 2026

REPOSITORIES: iProX

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USP7 facilitates brain tumor survival upon glucose deprivation by regulating phosphofructokinase muscle-type nuclear translocation in mice.

Wu Siyang S Cao Ruixiu R Huang Xiaolan X Feng Qiongni Q Zhang Yajuan Y Gao Hong H Tao Bangbao B Liang Ji J Yang Weiwei W

PLoS biology 20260312 3

Cancer cells reprogram the metabolic pathways to adapt to nutrient deficiency, while the underlying mechanism has not been fully understood. Phosphofructokinase 1 muscle type (PFKM) is the second rate-limiting step of glycolysis, catalyzing the phosphorylation of fructose 6-phosphate to fructose 1,6-bisphosphate. Here we show, using an orthotopic xenograft glioma mouse model, that PFKM is deubiquitinated and translocated into nucleus upon glucose deficiency, thereby activating fatty acid oxidati ...[more]

PMID: 41818193

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Gluconeogenesis using glycerol as a substrate in bloodstream-form Trypanosoma brucei

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2019-11-12 | PXD010334 | Pride

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PFKFB3 activates CAD to enhance de novo pyrimidine synthesis for cell growth

Project description:Aerobic glycolysis, which is also termed the Warburg effect, is one of the aberrant metabolic pathways in highly proliferating cells. Glycolysis provides glycolytic metabolites to support the generation of biomass, such as nucleotides, amino acids, and lipids. To date, no studies have explored interrelationships between glycolysis and other metabolic pathways. Phosphofructokinase-2/fructose-2,6-bisphosphatase 3 (PFKFB3) activates glycolysis by synthesizing fructose-2,6-bisphosphate (F2,6BP), which allosterically activates the rate-limiting enzyme 6-phosphofructo-1-kinase (PFK-1). In this study, we found that PFKFB3 directly interacts with and regulates the phosphorylation of carbamoyl-phosphate synthetase 2, aspartate transcarbamylase, and dihydroorotase (CAD), the enzyme catalyzing the first three steps of de novo pyrimidine synthesis. PFKFB3 inactivation reduced de novo pyrimidine synthesis, RNA and DNA production, and the growth of cancer and proliferative cells. Thus, the glycolytic activator PFKFB3 bridges glycolysis with pyrimidine synthesis, unites both glucose metabolism and nucleic acid metabolism, and contributes to cell proliferation under both physiological and pathological conditions.

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