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.
authors.affiliation: 1] Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine at Case Western Reserve University, Cleveland, Ohio, USA. [2] Department of Stem Cell Biology and Regenerative Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA.
authors.forename: William A
authors.initials: WA
authors.lastname: Flavahan
authors.forename: Qiulian
authors.initials: Q
authors.lastname: Wu
authors.forename: Masahiro
authors.initials: M
authors.lastname: Hitomi
authors.forename: Nasiha
authors.initials: N
authors.lastname: Rahim
authors.forename: Youngmi
authors.initials: Y
authors.lastname: Kim
authors.forename: Andrew E
authors.initials: AE
authors.lastname: Sloan
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Weil
authors.forename: Ichiro
authors.initials: I
authors.lastname: Nakano
authors.forename: Jann N
authors.initials: JN
authors.lastname: Sarkaria
authors.forename: Brett W
authors.initials: BW
authors.lastname: Stringer
authors.forename: Bryan W
authors.initials: BW
authors.lastname: Day
authors.forename: Meizhang
authors.initials: M
authors.lastname: Li
authors.forename: Justin D
authors.initials: JD
authors.lastname: Lathia
authors.forename: Jeremy N
authors.initials: JN
authors.lastname: Rich
authors.forename: Anita B
authors.initials: AB
authors.lastname: Hjelmeland
mesh_terms: D000818:Animals; D001692:Biological Transport / Q000502:physiology; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D001932:Brain Neoplasms / Q000378:metabolism* / Q000473:pathology; D002470:Cell Survival / Q000502:physiology; D005260:Female; D005947:Glucose / Q000172:deficiency* / Q000378:metabolism*; D051274:Glucose Transporter Type 3 / Q000096:biosynthesis*; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays / Q000379:methods
chemical_list: D051274:Glucose Transporter Type 3; C495687:SLC2A3 protein, human; D005947:Glucose