| Literature DB >> 29198914 |
Érika Cosset1, Sten Ilmjärv2, Valérie Dutoit3, Kathryn Elliott4, Tami von Schalscha4, Maria F Camargo4, Alexander Reiss4, Toshiro Moroishi5, Laetitia Seguin4, German Gomez4, Jung-Soon Moo5, Olivier Preynat-Seauve6, Karl-Heinz Krause2, Hervé Chneiweiss7, Jann N Sarkaria8, Kun-Liang Guan5, Pierre-Yves Dietrich3, Sara M Weis4, Paul S Mischel9, David A Cheresh10.
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. Published by Elsevier Inc.Entities:
Keywords: Glut3; cancer stem cells; glioblastoma; glucose metabolism; integrin
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Year: 2017 PMID： 29198914 PMCID： PMC5730343 DOI： 10.1016/j.ccell.2017.10.016
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743