Glut3 Addiction Is a Druggable Vulnerability for a Molecularly Defined Subpopulation of Glioblastoma
Résumé
While molecular subtypes of glioblastoma (GBM) are defined using gene expression and mutation profiles,
we identify a unique subpopulation based on addiction to the high-affinity glucose transporter, Glut3.
Although Glut3 is a known driver of a cancer stem cell phenotype, direct targeting is complicated by its
expression in neurons. Using established GBM lines and patient-derived stem cells, we identify a subset
of tumors within the ‘‘proneural’’ and ‘‘classical’’ subtypes that are addicted to aberrant signaling from integrin
avb3, which activates a PAK4-YAP/TAZ signaling axis to enhance Glut3 expression. This defined subpopulation
of GBM is highly sensitive to agents that disrupt this pathway, including the integrin antagonist
cilengitide, providing a targeted therapeutic strategy for this unique subset of GBM tumors.
Domaines
Sciences du Vivant [q-bio]| Origine | Fichiers produits par l'(les) auteur(s) |
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