Glut3 Addiction Is a Druggable Vulnerability for a Molecularly Defined Subpopulation of Glioblastoma - Sorbonne Université Access content directly
Journal Articles Cancer Cell Year : 2017

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

Erika Cosset

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 avb3, 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.
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hal-04021422 , version 1 (18-06-2023)

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Erika Cosset, Sten Ilmjärv, Valérie Dutoit, Kathryn Elliott, Tami von Schalscha, et al.. Glut3 Addiction Is a Druggable Vulnerability for a Molecularly Defined Subpopulation of Glioblastoma. Cancer Cell, 2017, 32, pp.856 - 868.e5. ⟨10.1016/j.ccell.2017.10.016⟩. ⟨hal-04021422⟩
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