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

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

342 Citations (Scopus)

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
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
Publication status	Published - Oct 2013
Externally published	Yes

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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

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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",

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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

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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.

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JO - NATURE NEUROSCIENCE

JF - NATURE NEUROSCIENCE

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

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