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

Krushna C. Patra, Qi Wang, Prashanth T. Bhaskar, Luke Miller, Zebin Wang, Will Wheaton, Navdeep Chandel, Markku Laakso, William J. Muller, Eric L. Allen, Abhishek K. Jha, Gromoslaw A. Smolen, Michelle F. Clasquin, R. Brooks Robey, Nissim Hay*

*Corresponding author for this work

Research output: Contribution to journalArticle

336 Scopus citations

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 invitro and invivo. 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.

Original languageEnglish (US)
Pages (from-to)213-228
Number of pages16
JournalCancer Cell
Volume24
Issue number2
DOIs
StatePublished - Aug 12 2013

ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research

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    Patra, K. C., Wang, Q., Bhaskar, P. T., Miller, L., Wang, Z., Wheaton, W., Chandel, N., Laakso, M., Muller, W. J., Allen, E. L., Jha, A. K., Smolen, G. A., Clasquin, M. F., Robey, R. B., & Hay, N. (2013). Hexokinase 2 is required for tumor initiation and maintenance and its systemic deletion is therapeutic in mouse models of cancer. Cancer Cell, 24(2), 213-228. https://doi.org/10.1016/j.ccr.2013.06.014