A role for GLUT3 in glioblastoma cell invasion that is not recapitulated by GLUT1
AuthorsLibby, Catherine J
Benavides, Gloria A
Fisher, Jennifer L
Williford, Sarah E
Tran, Anh Nhat
Gordon, Emily R
Jones, Amber B
Cooper, Sara J
Lasseigne, Brittany N
Augelli-Szafran, Corinne E
Hjelmeland, Anita B
UMass Chan AffiliationsMolecular, Cell and Cancer Biology
Document TypeJournal Article
MetadataShow full item record
AbstractThe multifaceted roles of metabolism in invasion have been investigated across many cancers. The brain tumor glioblastoma (GBM) is a highly invasive and metabolically plastic tumor with an inevitable recurrence. The neuronal glucose transporter 3 (GLUT3) was previously reported to correlate with poor glioma patient survival and be upregulated in GBM cells to promote therapeutic resistance and survival under restricted glucose conditions. It has been suggested that the increased glucose uptake mediated by GLUT3 elevation promotes survival of circulating tumor cells to facilitate metastasis. Here we suggest a more direct role for GLUT3 in promoting invasion that is not dependent upon changes in cell survival or metabolism. Analysis of glioma datasets demonstrated that GLUT3, but not GLUT1, expression was elevated in invasive disease. In human xenograft derived GBM cells, GLUT3, but not GLUT1, elevation significantly increased invasion in transwell assays, but not growth or migration. Further, there were no changes in glycolytic metabolism that correlated with invasive phenotypes. We identified the GLUT3 C-terminus as mediating invasion: substituting the C-terminus of GLUT1 for that of GLUT3 reduced invasion. RNA-seq analysis indicated changes in extracellular matrix organization in GLUT3 overexpressing cells, including upregulation of osteopontin. Together, our data suggest a role for GLUT3 in increasing tumor cell invasion that is not recapitulated by GLUT1, is separate from its role in metabolism and survival as a glucose transporter, and is likely broadly applicable since GLUT3 expression correlates with metastasis in many solid tumors.
SourceLibby CJ, Gc S, Benavides GA, Fisher JL, Williford SE, Zhang S, Tran AN, Gordon ER, Jones AB, Tuy K, Flavahan W, Gordillo J, Long A, Cooper SJ, Lasseigne BN, Augelli-Szafran CE, Darley-Usmar V, Hjelmeland AB. A role for GLUT3 in glioblastoma cell invasion that is not recapitulated by GLUT1. Cell Adh Migr. 2021 Dec;15(1):101-115. doi: 10.1080/19336918.2021.1903684. PMID: 33843470; PMCID: PMC8043167.
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/51927
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Except where otherwise noted, this item's license is described as © 2021 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.