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Title: Endothelial inhibition of the glycolytic activator PFKFB3 induces tumor vessel normalization, impairs metastasis and improves chemotherapy      
dateReleased:
11-17-2016
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.
privacy:
not applicable
aggregation:
instance of dataset
ID:
E-MTAB-4842
refinement:
raw
dateSubmitted:
01-16-2016
keywords:
functional genomics
dateModified:
11-07-2016
availability:
available
types:
gene expression
name:
Mus musculus
name:
case control design
accessURL: https://www.ebi.ac.uk/arrayexpress/files/E-MTAB-4842/E-MTAB-4842.raw.1.zip
storedIn:
ArrayExpress
qualifier:
gzip compressed
format:
TXT
accessType:
download
authentication:
none
authorization:
none
accessURL: https://www.ebi.ac.uk/arrayexpress/files/E-MTAB-4842/E-MTAB-4842.processed.1.zip
storedIn:
ArrayExpress
qualifier:
gzip compressed
format:
TXT
accessType:
download
authentication:
none
authorization:
none
abbreviation:
EBI
homePage: http://www.ebi.ac.uk/
ID:
SCR:004727
name:
European Bioinformatics Institute
homePage: https://www.ebi.ac.uk/arrayexpress/
ID:
SCR:002964
name:
ArrayExpress
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