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

Cosset, Erika; Ilmjarv, Sten; Dutoit Vallotton, Valérie; Elliott, Kathryn; von Schalscha, Tami; Camargo, Maria F.; Reiss, Alexander; Moroishi, Toshiro; Seguin, Laetitia; Gomez, German; Moo, Jung-Soon; Preynat-Seauve, Olivier; Krause, Karl-Heinz; Chneiweiss, Hervé; Sarkaria, Jann N; Guan, Kun-Liang; Dietrich, Pierre-Yves; Weis, Sara M; Mischel, Paul S; Cheresh, David A

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Title		Glut3 Addiction Is a Druggable Vulnerability for a Molecularly Defined Subpopulation of Glioblastoma
Authors		Cosset, Erika Ilmjarv, Sten Dutoit Vallotton, Valérie Elliott, Kathryn von Schalscha, Tami Camargo, Maria F. Reiss, Alexander Moroishi, Toshiro Seguin, Laetitia Gomez, German Moo, Jung-Soon Preynat-Seauve, Olivier Krause, Karl-Heinz Chneiweiss, Hervé Sarkaria, Jann N Guan, Kun-Liang Dietrich, Pierre-Yves Weis, Sara M Mischel, Paul S Cheresh, David A show all authors [1 - 20]
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		Animals — Antineoplastic Agents/pharmacology — Brain Neoplasms/metabolism/mortality — Cell Line, Tumor — Gene Expression Profiling — Glioblastoma/metabolism/mortality — Glucose Transporter Type 3/metabolism — Humans — Integrin alphaVbeta3/metabolism — Kaplan-Meier Estimate — Mice — Mice, Nude — Signal Transduction — Snake Venoms/pharmacology — Transcriptome — Xenograft Model Antitumor Assays
Identifiers		DOI: 10.1016/j.ccell.2017.10.016 PMID: 29198914
Full text		Article (Published version) (2.5 MB) - Limited access to UNIGE
Structures		Faculté de médecine / Section de médecine clinique / Département de médecine interne des spécialités Faculté de médecine / Section de médecine fondamentale / Département de pathologie et immunologie
Research groups		Radicaux libres et cellules souches embryonnaires (60) Immunothérapie des cancers (42)
Citation (ISO format)		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. https://archive-ouverte.unige.ch/unige:111356