@article{d18878212ded4990a3ca92128d2e4061,
title = "Glut3 Addiction Is a Druggable Vulnerability for a Molecularly Defined Subpopulation of Glioblastoma",
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. Cosset et al. identify a subset of glioblastoma within the proneural and the classical subtypes that are addicted to aberrant signaling from integrin αvβ3, which activates a PAK4-YAP/TAZ signaling axis to enhance Glut3 expression, and are sensitive to agents disrupting the pathway such as cilengitide.",
keywords = "Glut3, cancer stem cells, glioblastoma, glucose metabolism, integrin",
author = "{\'E}rika Cosset and Sten Ilmj{\"a}rv and Val{\'e}rie Dutoit and Kathryn Elliott and {von Schalscha}, Tami and Camargo, {Maria F.} and Alexander Reiss and Toshiro Moroishi and Laetitia Seguin and German Gomez and Moo, {Jung Soon} and Olivier Preynat-Seauve and Krause, {Karl Heinz} and Herv{\'e} Chneiweiss and Sarkaria, {Jann N.} and Guan, {Kun Liang} and Dietrich, {Pierre Yves} and Weis, {Sara M.} and Mischel, {Paul S.} and Cheresh, {David A.}",
note = "Funding Information: We thank B. Walsh and M. Hall for technical support. We also thank M. Yebra, M. Gozo, B. Walsh, J. Desgrosellier, T. Rakhshandehroo, J. Wawrzyniak, H. Wettersten, and members of Sarkaria and Chneiweiss lab for helpful discussions and collaboration as well as members of Dietrich and Dutoit lab for collaboration. E.C. was supported by The Fonds National Suisse , D.A.C. was supported by NCI - CA45726 . The authors also thank the Mayo SPORE in Brain Cancer ( CA108961 ) for financial support. Funding Information: We thank B. Walsh and M. Hall for technical support. We also thank M. Yebra, M. Gozo, B. Walsh, J. Desgrosellier, T. Rakhshandehroo, J. Wawrzyniak, H. Wettersten, and members of Sarkaria and Chneiweiss lab for helpful discussions and collaboration as well as members of Dietrich and Dutoit lab for collaboration. E.C. was supported by The Fonds National Suisse, D.A.C. was supported by NCI-CA45726. The authors also thank the Mayo SPORE in Brain Cancer (CA108961) for financial support. Publisher Copyright: {\textcopyright} 2017",
year = "2017",
month = dec,
day = "11",
doi = "10.1016/j.ccell.2017.10.016",
language = "English (US)",
volume = "32",
pages = "856--868.e5",
journal = "Cancer Cell",
issn = "1535-6108",
publisher = "Cell Press",
number = "6",
}