Skip to Main content Skip to Navigation
Journal articles

Glioblastoma invasion and cooption depend on IRE1α endoribonuclease activity

Abstract : IRE1α is an endoplasmic reticulum (ER)-resident transmembrane signaling protein and a cellular stress sensor. The protein harbors a cytosolic dual kinase/endoribonuclease activity required for adaptive responses to micro-environmental changes. In an orthotopic xenograft model of human glioma, invalidation of IRE1α RNase or/and kinase activities generated tumors with remarkably distinct phenotypes. Contrasting with the extensive angiogenesis observed in tumors derived from control cells, the double kinase/RNase invalidation reprogrammed mesenchymal differentiation of cancer cells and produced avascular and infiltrative glioblastomas with blood vessel co-option. In comparison, selective invalidation of IRE1α RNase did not compromise tumor angiogenesis but still elicited invasive features and vessel co-option. In vitro, IRE1α RNase deficient cells were also endowed with a higher ability to migrate. Constitutive activation of both enzymes led to wild-type-like lesions. The presence of IRE1α, but not its RNase activity, is therefore required for glioblastoma neovascularization, whereas invasion results only from RNase inhibition. In this model, two key mechanisms of tumor progression and cancer cell survival are functionally linked to IRE1α
Document type :
Journal articles
Complete list of metadatas

https://hal-univ-rennes1.archives-ouvertes.fr/hal-01197351
Contributor : Laurent Jonchère <>
Submitted on : Friday, September 11, 2015 - 3:12:59 PM
Last modification on : Tuesday, March 17, 2020 - 12:26:02 PM

Links full text

Identifiers

Citation

Arnaud Jabouille, Maylis Delugin, Raphäel Pineau, Alexandre Dubrac, Fabienne Soulet, et al.. Glioblastoma invasion and cooption depend on IRE1α endoribonuclease activity. Oncotarget, Impact journals, 2015, 6 (28), pp.24922-24934. ⟨10.18632/oncotarget.4679⟩. ⟨hal-01197351⟩

Share

Metrics