Regulation of hypoxia-induced autophagy in glioblastoma involves ATG9A.

ABSTRACT:

Background

Hypoxia is negatively associated with glioblastoma (GBM) patient survival and contributes to tumour resistance. Anti-angiogenic therapy in GBM further increases hypoxia and activates survival pathways. The aim of this study was to determine the role of hypoxia-induced autophagy in GBM.

Methods

Pharmacological inhibition of autophagy was applied in combination with bevacizumab in GBM patient-derived xenografts (PDXs). Sensitivity towards inhibitors was further tested in vitro under normoxia and hypoxia, followed by transcriptomic analysis. Genetic interference was done using ATG9A-depleted cells.

Results

We find that GBM cells activate autophagy as a survival mechanism to hypoxia, although basic autophagy appears active under normoxic conditions. Although si

SUBMITTER: Abdul Rahim SA 

PROVIDER: S-EPMC5590001 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature