The hexokinase “HKDC1” interaction with the mitochondria is essential for liver cancer progression

Md. Wasim Khan; Alexander R. Terry; Medha Priyadarshini; Vladimir Ilievski; Zeenat Farooq; Grace Guzman; Jose Cordoba-Chacon; Issam Ben-Sahra; Barton Wicksteed; Brian T. Layden

doi:10.1038/s41419-022-04999-z

Cell Death and Disease (Jul 2022)

The hexokinase “HKDC1” interaction with the mitochondria is essential for liver cancer progression

Md. Wasim Khan,
Alexander R. Terry,
Medha Priyadarshini,
Vladimir Ilievski,
Zeenat Farooq,
Grace Guzman,
Jose Cordoba-Chacon,
Issam Ben-Sahra,
Barton Wicksteed,
Brian T. Layden

Affiliations

Md. Wasim Khan: Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Illinois at Chicago
Alexander R. Terry: Department of Biochemistry and Molecular Genetics, College of Medicine, University of Illinois at Chicago
Medha Priyadarshini: Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Illinois at Chicago
Vladimir Ilievski: Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Illinois at Chicago
Zeenat Farooq: Division of Endocrinology, Diabetes and Metabolism, Department 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
Jose Cordoba-Chacon: Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Illinois at Chicago
Issam Ben-Sahra: Department of Biochemistry and Molecular Genetics, Feinberg School of Medicine, Northwestern University
Barton Wicksteed: Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Illinois at Chicago
Brian T. Layden: Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Illinois at Chicago

DOI: https://doi.org/10.1038/s41419-022-04999-z
Journal volume & issue: Vol. 13, no. 7
pp. 1 – 17

Abstract

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Mitochondrial interaction of HKDC1 is essential for its pro-proliferative role in LC. When HKDC1 is ablated in liver cancer cells, mitochondrial dysfunction occurs which results in decrease ATP in the cells. The cancer cells react to decreased cellular energy by increasing glucose uptake. Also due to mitochondrial dysfunction there is enhanced ER stress and ER-mitochondrial interaction, leading to more calcium flux into the mitochondria. This multi-pronged effects of HKDC1 ablation leads to decreased cellular proliferation in LC.

Published in Cell Death and Disease

ISSN: 2041-4889 (Online)
Publisher: Nature Publishing Group
Country of publisher: United Kingdom
LCC subjects: Science: Biology (General): Cytology
Website: http://www.nature.com/cddis/index.html

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