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PFKFB3 inhibits fructose metabolism in pulmonary microvascular endothelial cells

ABSTRACT: We hypothesized that PFKFB3 inhibits fructose metabolism in pulmonary microvascular endothelial cells (PMVECs) and found that PFKFB3 knockout cells survive better than wild type cells in fructose-rich media, more so under hypoxia. Our findings indicate that PFKFB3 is a molecular switch that controls glucose versus fructose utilization in glycolysis and help to better understand lung endothelial cell metabolism during respiratory failure.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE230660 | GEO | 2023/08/01

REPOSITORIES: GEO

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Gene expression data of PFKFB3 KD in SMMC7721 cell line

Project description:Overexpression of 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3), a key molecule of glucose metabolism in cytoplasm, was found in various tumors. Emerging evidence suggested that PFKFB3 also located in nucleus and shown regulatory functions other than glycolysis. In this study, we found that PFKFB3 expression is associated with hepatocellular carcinoma (HCC) growth and mainly located in the nucleus of tumor cells. PFKFB3 overexpression was associated with large tumor size, and poor survival of patients with HCC. Knockdown of PFKFB3 inhibited HCC growth, not only by reducing glucose consuming but also damaging DNA repair function leading to G2/M phase arrest and apoptosis. Therefore, we performed a cDNA microarray in PFKFB3 knockdown SMMC7721 cells.

2018-03-01 | GSE106603 | GEO

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2023-09-13 | PXD041780 | Pride

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Project description:Abnormal tumor vessels promote metastasis and impair chemotherapy. Hence, tumor vessel normalization (TVN) by targeting endothelial cells (ECs) is emerging as anti-cancer treatment. Here, we show that tumor ECs (TECs) have a hyper-glycolytic metabolism, shunting glycolytic intermediates to nucleotide synthesis. EC haplo-deficiency or blockade of the glycolytic activator PFKFB3 did not affect tumor growth, but reduced cancer cell intra- and extravasation and metastasis by normalizing tumor vessels, which improved vessel maturation and perfusion. Mechanistically, PFKFB3 inhibition tightened the vascular barrier by reducing VE-cadherin endocytosis in ECs and rendering glycolytic pericytes more quiescent; it also lowered the expression of cancer cell adhesion molecules in ECs. Additionally, PFKFB3-blockade treatment improved chemotherapy. Considering TEC metabolism for anti-cancer treatment might thus merit further attention.

2016-11-17 | E-MTAB-4842 | biostudies-arrayexpress

Genome wide analysis of differential gene expression of PFKFB3 under- or overexpression upon inhibition or activation of notch signaling in endothelial cells

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2013-08-01 | E-GEOD-45750 | biostudies-arrayexpress

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2022-08-22 | GSE211648 | GEO

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2023-11-02 | E-MEXP-3956 | biostudies-arrayexpress

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