This phenomenon is mediated by transcriptional upregulation of GPR133 in hypoxia via direct binding of hypoxia-inducible factor 1α (HIF-1α) to its promoter.49 The finding suggests that GPR133 is not only a necessary component of GBM growth, but it may also mediate the tumor’s cellular response to hypoxia. This evidence concerns the gene ADGRD1 and glioblastoma.