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

Elliott, Kathryn
von Schalscha, Tami
Camargo, Maria F.
Reiss, Alexander
Moroishi, Toshiro
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Published in Cancer Cell. 2017, vol. 32, no. 6, p. 856-868.e5
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 αvβ3, 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.
Keywords AnimalsAntineoplastic Agents/pharmacologyBrain Neoplasms/metabolism/mortalityCell Line, TumorGene Expression ProfilingGlioblastoma/metabolism/mortalityGlucose Transporter Type 3/metabolismHumansIntegrin alphaVbeta3/metabolismKaplan-Meier EstimateMiceMice, NudeSignal TransductionSnake Venoms/pharmacologyTranscriptomeXenograft Model Antitumor Assays
PMID: 29198914
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Research groups Génomique et métagénomique des produits sanguins labiles (956)
Immunothérapie des cancers (42)
Radicaux libres et cellules souches embryonnaires (60)
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COSSET, Erika et al. Glut3 Addiction Is a Druggable Vulnerability for a Molecularly Defined Subpopulation of Glioblastoma. In: Cancer Cell, 2017, vol. 32, n° 6, p. 856-868.e5. doi: 10.1016/j.ccell.2017.10.016 https://archive-ouverte.unige.ch/unige:111356

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Deposited on : 2018-11-23

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