Brain tumor initiating cells adapt to restricted nutrition through preferential glucose uptake

William A. Flavahan; Qiulian Wu; Masahiro Hitomi; Nasiha Rahim; Youngmi Kim; Andrew E. Sloan; Robert J. Weil; Ichiro Nakano; Jann N. Sarkaria; Brett W. Stringer; Bryan W. Day; Meizhang Li; Justin D. Lathia; Jeremy N. Rich; Anita B. Hjelmeland

doi:10.1038/nn.3510

Brain tumor initiating cells adapt to restricted nutrition through preferential glucose uptake

William A. Flavahan, Qiulian Wu, Masahiro Hitomi, Nasiha Rahim, Youngmi Kim, Andrew E. Sloan, Robert J. Weil, Ichiro Nakano, Jann N. Sarkaria, Brett W. Stringer, Bryan W. Day, Meizhang Li, Justin D. Lathia, Jeremy N. Rich, Anita B. Hjelmeland

Radiation Oncology

Research output: Contribution to journal › Article › peer-review

248 Scopus citations

Abstract

Like all cancers, brain tumors require a continuous source of energy and molecular resources for new cell production. In normal brain, glucose is an essential neuronal fuel, but the blood-brain barrier limits its delivery. We now report that nutrient restriction contributes to tumor progression by enriching for brain tumor initiating cells (BTICs) owing to preferential BTIC survival and to adaptation of non-BTICs through acquisition of BTIC features. BTICs outcompete for glucose uptake by co-opting the high affinity neuronal glucose transporter, type 3 (Glut3, SLC2A3). BTICs preferentially express Glut3, and targeting Glut3 inhibits BTIC growth and tumorigenic potential. Glut3, but not Glut1, correlates with poor survival in brain tumors and other cancers; thus, tumor initiating cells may extract nutrients with high affinity. As altered metabolism represents a cancer hallmark, metabolic reprogramming may maintain the tumor hierarchy and portend poor prognosis.

Original language	English (US)
Pages (from-to)	1373-1382
Number of pages	10
Journal	Nature Neuroscience
Volume	16
Issue number	10
DOIs	https://doi.org/10.1038/nn.3510
State	Published - Oct 2013

ASJC Scopus subject areas

General Neuroscience

Access to Document

10.1038/nn.3510

Cite this

Flavahan, W. A., Wu, Q., Hitomi, M., Rahim, N., Kim, Y., Sloan, A. E., Weil, R. J., Nakano, I., Sarkaria, J. N., Stringer, B. W., Day, B. W., Li, M., Lathia, J. D., Rich, J. N., & Hjelmeland, A. B. (2013). Brain tumor initiating cells adapt to restricted nutrition through preferential glucose uptake. Nature Neuroscience, 16(10), 1373-1382. https://doi.org/10.1038/nn.3510

@article{ad10206d2dcb46b592e7d7181d138ee8,

title = "Brain tumor initiating cells adapt to restricted nutrition through preferential glucose uptake",

abstract = "Like all cancers, brain tumors require a continuous source of energy and molecular resources for new cell production. In normal brain, glucose is an essential neuronal fuel, but the blood-brain barrier limits its delivery. We now report that nutrient restriction contributes to tumor progression by enriching for brain tumor initiating cells (BTICs) owing to preferential BTIC survival and to adaptation of non-BTICs through acquisition of BTIC features. BTICs outcompete for glucose uptake by co-opting the high affinity neuronal glucose transporter, type 3 (Glut3, SLC2A3). BTICs preferentially express Glut3, and targeting Glut3 inhibits BTIC growth and tumorigenic potential. Glut3, but not Glut1, correlates with poor survival in brain tumors and other cancers; thus, tumor initiating cells may extract nutrients with high affinity. As altered metabolism represents a cancer hallmark, metabolic reprogramming may maintain the tumor hierarchy and portend poor prognosis.",

author = "Flavahan, {William A.} and Qiulian Wu and Masahiro Hitomi and Nasiha Rahim and Youngmi Kim and Sloan, {Andrew E.} and Weil, {Robert J.} and Ichiro Nakano and Sarkaria, {Jann N.} and Stringer, {Brett W.} and Day, {Bryan W.} and Meizhang Li and Lathia, {Justin D.} and Rich, {Jeremy N.} and Hjelmeland, {Anita B.}",

year = "2013",

month = oct,

doi = "10.1038/nn.3510",

language = "English (US)",

volume = "16",

pages = "1373--1382",

journal = "Nature Neuroscience",

issn = "1097-6256",

publisher = "Nature Publishing Group",

number = "10",

}

TY - JOUR

T1 - Brain tumor initiating cells adapt to restricted nutrition through preferential glucose uptake

AU - Flavahan, William A.

AU - Wu, Qiulian

AU - Hitomi, Masahiro

AU - Rahim, Nasiha

AU - Kim, Youngmi

AU - Sloan, Andrew E.

AU - Weil, Robert J.

AU - Nakano, Ichiro

AU - Sarkaria, Jann N.

AU - Stringer, Brett W.

AU - Day, Bryan W.

AU - Li, Meizhang

AU - Lathia, Justin D.

AU - Rich, Jeremy N.

AU - Hjelmeland, Anita B.

PY - 2013/10

Y1 - 2013/10

N2 - Like all cancers, brain tumors require a continuous source of energy and molecular resources for new cell production. In normal brain, glucose is an essential neuronal fuel, but the blood-brain barrier limits its delivery. We now report that nutrient restriction contributes to tumor progression by enriching for brain tumor initiating cells (BTICs) owing to preferential BTIC survival and to adaptation of non-BTICs through acquisition of BTIC features. BTICs outcompete for glucose uptake by co-opting the high affinity neuronal glucose transporter, type 3 (Glut3, SLC2A3). BTICs preferentially express Glut3, and targeting Glut3 inhibits BTIC growth and tumorigenic potential. Glut3, but not Glut1, correlates with poor survival in brain tumors and other cancers; thus, tumor initiating cells may extract nutrients with high affinity. As altered metabolism represents a cancer hallmark, metabolic reprogramming may maintain the tumor hierarchy and portend poor prognosis.

AB - Like all cancers, brain tumors require a continuous source of energy and molecular resources for new cell production. In normal brain, glucose is an essential neuronal fuel, but the blood-brain barrier limits its delivery. We now report that nutrient restriction contributes to tumor progression by enriching for brain tumor initiating cells (BTICs) owing to preferential BTIC survival and to adaptation of non-BTICs through acquisition of BTIC features. BTICs outcompete for glucose uptake by co-opting the high affinity neuronal glucose transporter, type 3 (Glut3, SLC2A3). BTICs preferentially express Glut3, and targeting Glut3 inhibits BTIC growth and tumorigenic potential. Glut3, but not Glut1, correlates with poor survival in brain tumors and other cancers; thus, tumor initiating cells may extract nutrients with high affinity. As altered metabolism represents a cancer hallmark, metabolic reprogramming may maintain the tumor hierarchy and portend poor prognosis.

UR - http://www.scopus.com/inward/record.url?scp=84884893986&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84884893986&partnerID=8YFLogxK

U2 - 10.1038/nn.3510

DO - 10.1038/nn.3510

M3 - Article

C2 - 23995067

AN - SCOPUS:84884893986

SN - 1097-6256

VL - 16

SP - 1373

EP - 1382

JO - Nature Neuroscience

JF - Nature Neuroscience

IS - 10

ER -

Brain tumor initiating cells adapt to restricted nutrition through preferential glucose uptake

Abstract

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this