KRAS-Dependent Glycolytic Reprogramming of Endothelial Cells in Sporadic Arteriovenous Malformations

ABSTRACT: Somatic activating KRAS mutations in endothelial cells are the predominant cause of sporadic brain arteriovenous malformations (bAVMs) and also occur in sporadic extracranial AVMs. We found that KRAS-G12V expression in the endothelium increased angiogenesis, which was accompanied by enhanced glucose uptake and glycolytic flux. Mechanistically, this increase in glycolysis was facilitated by enhanced membrane localization of glucose transporters (e.g., GLUT1) and induction of hexokinase-2 (HK2) expression. Importantly, RNA-sequencing and proteomics revealed that HK2 appeared to be the only glycolytic component elevated. Analysis of single-cell RNA-sequencing data and immunofluorescence staining confirmed that HK2 was elevated in mouse and human bAVMs. Critically, either pharmacologic inhibit

SUBMITTER: Ruilin Wu 

PROVIDER: S-SCDT-10_1038-S44321-026-00383-Y | biostudies-other |

REPOSITORIES: biostudies-other