Hexokinase-2 depletion inhibits glycolysis and induces oxidative phosphorylation in hepatocellular carcinoma and sensitizes to metformin

Dannielle DeWaal; Veronique Nogueira; Alexander R. Terry; Krushna C. Patra; Sang-Min Jeon; Grace Guzman; Jennifer Au; Christopher P. Long; Maciek R. Antoniewicz; Nissim Hay

doi:10.1038/s41467-017-02733-4

Nature Communications (Jan 2018)

Hexokinase-2 depletion inhibits glycolysis and induces oxidative phosphorylation in hepatocellular carcinoma and sensitizes to metformin

Dannielle DeWaal,
Veronique Nogueira,
Alexander R. Terry,
Krushna C. Patra,
Sang-Min Jeon,
Grace Guzman,
Jennifer Au,
Christopher P. Long,
Maciek R. Antoniewicz,
Nissim Hay

Affiliations

Dannielle DeWaal: Department of Biochemistry and Molecular Genetics, College of Medicine, University of Illinois at Chicago
Veronique Nogueira: Department of Biochemistry and Molecular Genetics, College of Medicine, University of Illinois at Chicago
Alexander R. Terry: Department of Biochemistry and Molecular Genetics, College of Medicine, University of Illinois at Chicago
Krushna C. Patra: Department of Biochemistry and Molecular Genetics, College of Medicine, University of Illinois at Chicago
Sang-Min Jeon: Department of Biochemistry and Molecular Genetics, College of Medicine, University of Illinois at Chicago
Grace Guzman: Department of Pathology, College of Medicine, Cancer Center, University of Illinois Hospital and Health Science Chicago
Jennifer Au: Department of Chemical and Biomolecular Engineering, Metabolic Engineering and Systems Biology Laboratory, University of Delaware
Christopher P. Long: Department of Chemical and Biomolecular Engineering, Metabolic Engineering and Systems Biology Laboratory, University of Delaware
Maciek R. Antoniewicz: Department of Chemical and Biomolecular Engineering, Metabolic Engineering and Systems Biology Laboratory, University of Delaware
Nissim Hay: Department of Biochemistry and Molecular Genetics, College of Medicine, University of Illinois at Chicago

DOI: https://doi.org/10.1038/s41467-017-02733-4
Journal volume & issue: Vol. 9, no. 1
pp. 1 – 14

Abstract

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Hexokinase 2 (HK2) is selectively upregulated in hepatocellular carcinoma (HCC). Here the authors show that HK2 ablation decreases glycolysis and triggers oxidative phosphorylation (OXPHO) rendering HCC more susceptible to the OXPHO inhibitor metformin and to the FDA-approved drug sorafenib.

Published in Nature Communications

ISSN: 2041-1723 (Online)
Publisher: Nature Portfolio
Country of publisher: United Kingdom
LCC subjects: Science
Website: https://www.nature.com/ncomms/

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