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Xu S, Catapang A, Braas D, et al. A precision therapeutic strategy for hexokinase 1-null, hexokinase 2-positive cancers. Cancer Metab. 2018;6:7doi: 10.1186/s40170-018-0181-8.
Xu, S., Catapang, A., Braas, D., Stiles, L., Doh, H. M., Lee, J. T., Graeber, T. G., Damoiseaux, R., Shirihai, O., & Herschman, H. R. (2018). A precision therapeutic strategy for hexokinase 1-null, hexokinase 2-positive cancers. Cancer & metabolism, 67. https://doi.org/10.1186/s40170-018-0181-8
Xu, Shili, et al. "A precision therapeutic strategy for hexokinase 1-null, hexokinase 2-positive cancers." Cancer & metabolism vol. 6 (2018): 7. doi: https://doi.org/10.1186/s40170-018-0181-8
Xu S, Catapang A, Braas D, Stiles L, Doh HM, Lee JT, Graeber TG, Damoiseaux R, Shirihai O, Herschman HR. A precision therapeutic strategy for hexokinase 1-null, hexokinase 2-positive cancers. Cancer Metab. 2018 Jun 28;6:7. doi: 10.1186/s40170-018-0181-8. eCollection 2018. PMID: 29988332; PMCID: PMC6022704.
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Cancer Metab. 2018 Jun 28;6:7. doi: 10.1186/s40170-018-0181-8. eCollection 2018.

A precision therapeutic strategy for hexokinase 1-null, hexokinase 2-positive cancers.

Cancer & metabolism

Shili Xu, Arthur Catapang, Daniel Braas, Linsey Stiles, Hanna M Doh, Jason T Lee, Thomas G Graeber, Robert Damoiseaux, Orian Shirihai, Harvey R Herschman

Affiliations

  1. 1Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095 USA.
  2. 3UCLA Metabolomics Center, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095 USA.
  3. 6Division of Endocrinology, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095 USA.
  4. 4Crump Institute for Molecular Imaging, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095 USA.
  5. 5Jonsson Comprehensive Cancer Center, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095 USA.
  6. 7California NanoSystems Institute, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095 USA.
  7. 2Department of Biological Chemistry, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095 USA.
  8. 8Molecular Biology Institute, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095 USA.

PMID: 29988332 PMCID: PMC6022704 DOI: 10.1186/s40170-018-0181-8

Abstract

BACKGROUND: Precision medicine therapies require identification of unique molecular cancer characteristics. Hexokinase (HK) activity has been proposed as a therapeutic target; however, different hexokinase isoforms have not been well characterized as alternative targets. While HK2 is highly expressed in the majority of cancers, cancer subtypes with differential HK1 and HK2 expression have not been characterized for their sensitivities to HK2 silencing.

METHODS: HK1 and HK2 expression in the Cancer Cell Line Encyclopedia dataset was analyzed. A doxycycline-inducible shRNA silencing system was used to examine the effect of HK2 knockdown in cultured cells and in xenograft models of HK1

RESULTS: Most tumors express both HK1 and HK2, and subsets of cancers from a wide variety of tissues of origin express only HK2. Unlike HK1

CONCLUSIONS: The HK1

Keywords: Cancer; Diphenyleneiodonium; Fatty acid oxidation; Glycolysis; Hexokinase 2; Liver cancer; Mitochondria complex-I; Oxidative phosphorylation; Perhexiline; Precision medicine; Synthetic lethality; Warburg effect

Conflict of interest statement

Not applicable.The authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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