Hexokinase 2 Is Required for Tumor Initiation and Maintenance and Its Systemic Deletion Is Therapeutic in Mouse Models of Cancer

被引：708

作者：

Patra, Krushna C. ^{[1
]}

Wang, Qi ^{[1
]}

Bhaskar, Prashanth T. ^{[1
]}

Miller, Luke ^{[1
]}

Wang, Zebin ^{[1
]}

Wheaton, Will ^{[2
]}

Chandel, Navdeep ^{[2
]}

Laakso, Markku ^{[3
]}

Muller, William J. ^{[4
]}

Allen, Eric L. ^{[5
]}

Jha, Abhishek K. ^{[5
]}

Smolen, Gromoslaw A. ^{[5
]}

Clasquin, Michelle F. ^{[5
]}

Robey, R. Brooks ^{[6
,7
]}

Hay, Nissim ^{[1
,8
]}

机构：

[1] Univ Illinois, Coll Med, Dept Biochem & Mol Genet, Chicago, IL 60607 USA

[2] Northwestern Univ, Sch Med, Dept Med, Div Pulm & Crit Care Med, Chicago, IL 60611 USA

[3] Univ Eastern Finland, Dept Med, Kuopio 70100, Finland

[4] McGill Univ, Goodman Canc Res Ctr, Dept Biochem, Montreal, PQ H3A 1A3, Canada

[5] Agios Pharmaceut, Cambridge, MA 02139 USA

[6] Vet Affairs Med Ctr, White River Jct, VT 05009 USA

[7] Dartmouth Med Sch, Geisel Sch Med, Hanover, NH 03755 USA

[8] Jesse Brown VA Med Ctr, Res & Dev Sect, Chicago, IL 60612 USA

来源：

CANCER CELL | 2013年 / 24卷 / 02期

关键词：

GLUTAMINE-METABOLISM; AEROBIC GLYCOLYSIS; GLUCOSE; EXPRESSION; SERINE; CELLS; MICE; ADENOCARCINOMA; PROGRESSION; TOXICITY;

D O I：

10.1016/j.ccr.2013.06.014

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：213 / 228

页数：16

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