MCT4 regulates de novo pyrimidine biosynthesis in GBM in a lactate-independent manner.

ABSTRACT:

Background

Necrotic foci with surrounding hypoxic cellular pseudopalisades and microvascular hyperplasia are histological features found in glioblastoma (GBM). We have previously shown that monocarboxylate transporter 4 (MCT4) is highly expressed in necrotic/hypoxic regions in GBM and that increased levels of MCT4 are associated with worse clinical outcomes.

Methods

A combined transcriptomics and metabolomics analysis was performed to study the effects of MCT4 depletion in hypoxic GBM neurospheres. Stable and inducible MCT4-depletion systems were used to evaluate the effects of and underlining mechanisms associated with MCT4 depletion in vitro and in vivo, alone and in combination with radiation.

Results

This study establishes that conditional depletion of MCT4 profou

SUBMITTER: Spina R 

PROVIDER: S-EPMC6979491 | biostudies-literature | 2020 Jan-Dec

REPOSITORIES: biostudies-literature