NOVEL HEXOKINASE-2 ASSOCIATED INFLAMMATORY PROCESSES IN THE GLIOBLASTOMA TUMOUR MICROENVIRONMENT

Deregulation of cellular metabolism is a hallmark of cancer, in which tumour cells upregulate glycolysis and preferentially ferment glucose to lactate (rather than pyruvate) in the 'Warburg effect'. Tumour-specific upregulation of hexokinase 2 (HK2), which catalyses the first rate-limiting step of glycolysis, has been established as key to this Warburg metabolism. Interrogating the impact of HK2 expression inhibition upon the glioblastoma transcriptome has the potential to uncover a number of novel canonical/non-canonical relationships that could serve as future co-therapeutic targets. To investigate this, we employed RNAseq to compare the expression profiles of glioblastoma cell cultures transfected with either HK2-targeted or non-targeting negative-control siRNA, thereby identifying genes differentially expressed specifically following HK2KD. Gene ontology category enrichment (GOSeq, Enrichment map) and STRING protein-protein interaction analysis of genes identified to be differentially expressed post HK2 knockdown (HK2KD) highlighted potential non-canonical roles for HK2 in regulating inflammatory, immune and angiogenesis-related processes within the glioblastoma tumour microenvironment.