Surprisingly, while IRE1 in malignant glioma is positively associated with the upregulation of proangiogenic factors such as VEGF-A, IL-1β, IL-6, and IL-8, it induces significant downregulation of proteins linked to mesenchymal differentiation and glioma invasiveness, such as secreted protein acidic and rich in cysteine (SPARC), decorin, and thrombospondin-1 [227,228], strongly suggesting that a comprehensive analysis of the IRE1/XBP1 axis is required to determine the relationship between invasiveness and angiogenesis. This evidence concerns the gene ERN1 and central nervous system cancer.