Format

Send to

Choose Destination
Cancer Cell. 2017 Dec 11;32(6):856-868.e5. doi: 10.1016/j.ccell.2017.10.016. Epub 2017 Nov 30.

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

Author information

1
Department of Pathology, Moores Cancer Center, Sanford Consortium for Regenerative Medicine, University of California San Diego, La Jolla, CA 92037, USA. Electronic address: erika.cosset@unige.ch.
2
Department of Pathology and Immunology, Medical School, University of Geneva, Geneva, Vital-IT Group, SIB Swiss Institute of Bioinformatics, Lausanne, Switzerland.
3
Laboratory of Tumor Immunology, Centre of Oncology, Geneva University Hospitals, University of Geneva, Geneva, Switzerland.
4
Department of Pathology, Moores Cancer Center, Sanford Consortium for Regenerative Medicine, University of California San Diego, La Jolla, CA 92037, USA.
5
Department of Pharmacology, Moores Cancer Center, Sanford Consortium for Regenerative Medicine, University of California San Diego, La Jolla, CA 92037, USA.
6
Division of Hematology, Departments of Internal Medicine and Human Protein Science, Faculty of Medicine, University of Geneva, Geneva, Switzerland.
7
INSERM U1310, Sorbonne Universités, Paris, France.
8
Department of Radiation Oncology, Mayo Clinic, Rochester, MN 55905, USA.
9
Ludwig Institute for Cancer Research, Department of Pathology, Moores Cancer Center, University of California San Diego, La Jolla, CA 92093, USA.
10
Department of Pathology, Moores Cancer Center, Sanford Consortium for Regenerative Medicine, University of California San Diego, La Jolla, CA 92037, USA. Electronic address: dcheresh@ucsd.edu.

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:

Glut3; cancer stem cells; glioblastoma; glucose metabolism; integrin

PMID:
29198914
PMCID:
PMC5730343
DOI:
10.1016/j.ccell.2017.10.016
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center