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Glut3 Addiction Is a Druggable Vulnerability for a Molecularly Defined Subpopulation of Glioblastoma

Authors
Cosset, E; Ilmjarv, S; Dutoit, V; Elliott, K; von Schalscha, T; Camargo, MF; Reiss, A; Moroishi, T; Seguin, L; Gomez, G; Moo, JS; Preynat-Seauve, O; Krause, KH; Chneiweiss, H; Sarkaria, JN; Guan, KL; Dietrich, PY; Weis, SM; Mischel, PS; Cheresh, DA
Citation
Cancer cell, 32(6):856-868.e1–e5, 2017
Journal Title
Cancer cell
ISSN
1535-61081878-3686
Abstract
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 alphavbeta3, 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.
MeSH terms
AnimalsAntineoplastic Agents/pharmacologyBrain Neoplasms/metabolism*Brain Neoplasms/mortalityCell Line, TumorGene Expression ProfilingGlioblastoma/metabolism*Glioblastoma/mortalityGlucose Transporter Type 3/metabolism*HumansIntegrin alphaVbeta3/metabolism*Kaplan-Meier EstimateMiceMice, NudeSignal TransductionSnake Venoms/pharmacologyTranscriptome*Xenograft Model Antitumor Assays
DOI
10.1016/j.ccell.2017.10.016
PMID
29198914
Appears in Collections:
Journal Papers > Research Organization > Genomic Instability Research Center
AJOU Authors
모, 정순
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