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Cancer Cell. 2013 Aug 12;24(2):213-228. doi: 10.1016/j.ccr.2013.06.014. Epub 2013 Aug 1.

Hexokinase 2 is required for tumor initiation and maintenance and its systemic deletion is therapeutic in mouse models of cancer.

Author information

1
Department of Biochemistry and Molecular Genetics, College of Medicine, University of Illinois at Chicago, Chicago, IL 60607, USA.
2
Department of Medicine, Division of Pulmonary and Critical Care Medicine, Northwestern University Medical School, Chicago, IL 60611, USA.
3
Department of Medicine, University of Eastern Finland, Kuopio, Finland.
4
Department of Biochemistry, Goodman Cancer Research Centre, McGill University, Montreal, Quebec H3A 1A3, Canada.
5
Agios Pharmaceuticals, 38 Sidney Street, Cambridge, MA 02139, USA.
6
Veterans Affairs Medical Center, White River Junction, VT 05009, USA.
7
Geisel School of Medicine at Dartmouth Medical School, Hanover, NH 03755, USA.
8
Research & Development Section, Jesse Brown VA Medical Center, Chicago, IL 60612, USA.
#
Contributed equally

Erratum in

  • Cancer Cell. 2013 Sep 9;24(3):399.

Abstract

Accelerated glucose metabolism is a common feature of cancer cells. Hexokinases catalyze the first committed step of glucose metabolism. Hexokinase 2 (HK2) is expressed at high level in cancer cells, but only in a limited number of normal adult tissues. Using Hk2 conditional knockout mice, we showed that HK2 is required for tumor initiation and maintenance in mouse models of KRas-driven lung cancer, and ErbB2-driven breast cancer, despite continued HK1 expression. Similarly, HK2 ablation inhibits the neoplastic phenotype of human lung and breast cancer cells in vitro and in vivo. Systemic Hk2 deletion is therapeutic in mice bearing lung tumors without adverse physiological consequences. Hk2 deletion in lung cancer cells suppressed glucose-derived ribonucleotides and impaired glutamine-derived carbon utilization in anaplerosis.

PMID:
23911236
PMCID:
PMC3753022
DOI:
10.1016/j.ccr.2013.06.014
[Indexed for MEDLINE]
Free PMC Article
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