Aiding Cancer’s “Sweet Tooth”: Role of Hexokinases in Metabolic Reprogramming

Author:

Farooq Zeenat1,Ismail Hagar1ORCID,Bhat Sheraz Ahmad1,Layden Brian T.12,Khan Md. Wasim1ORCID

Affiliation:

1. Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, The University of Illinois at Chicago, Chicago, IL 60612, USA

2. Jesse Brown Veterans Affairs Medical Center, Chicago, IL 60612, USA

Abstract

Hexokinases (HKs) convert hexose sugars to hexose-6-phosphate, thus trapping them inside cells to meet the synthetic and energetic demands. HKs participate in various standard and altered physiological processes, including cancer, primarily through the reprogramming of cellular metabolism. Four canonical HKs have been identified with different expression patterns across tissues. HKs 1–3 play a role in glucose utilization, whereas HK 4 (glucokinase, GCK) also acts as a glucose sensor. Recently, a novel fifth HK, hexokinase domain containing 1 (HKDC1), has been identified, which plays a role in whole-body glucose utilization and insulin sensitivity. Beyond the metabolic functions, HKDC1 is differentially expressed in many forms of human cancer. This review focuses on the role of HKs, particularly HKDC1, in metabolic reprogramming and cancer progression.

Funder

DOD Career Development

VA Merit Review Award

NIH

Publisher

MDPI AG

Subject

Paleontology,Space and Planetary Science,General Biochemistry, Genetics and Molecular Biology,Ecology, Evolution, Behavior and Systematics

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