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Title: Regulatory role of hexokinase 2 in modulating head and neck tumorigenesis
Authors: Li, WC
Huang, C 
Hsieh, YT
Chen, TY
Cheng, LH
Chen, CY
Liu, CJ
Chen, HM
Huang, CL
Lo, JF
Chang, KW
Issue Date: 2020
Source: Frontiers in oncology, 3 Mar. 2020, v. 10, 176, p. 1-11
Abstract: To support great demand of cell growth, cancer cells preferentially obtain energy and biomacromolecules by glycolysis over mitochondrial oxidative phosphorylation (OxPhos). Among all glycolytic enzymes, hexokinase (HK), a rate-limiting enzyme at the first step of glycolysis to catalyze cellular glucose into glucose-6-phosphate, is herein emphasized. Four HK isoforms, HK1-HK4, were discovered in nature. It was shown that HK2 expression is enriched in many tumor cells and correlated with poorer survival rates in most neoplastic cells. HK2-mediated regulations for cell malignancy and mechanistic cues in regulating head and neck tumorigenesis, however, are not fully elucidated. Cellular malignancy index, such as cell growth, cellular motility, and treatment sensitivity, and molecular alterations were determined in HK2-deficient head and neck squamous cell carcinoma (HNSCC) cells. By using various cancer databases, HK2, but not HK1, positively correlates with HNSCC progression in a stage-dependent manner. A high HK2 expression was detected in head and neck cancerous tissues compared with their normal counterparts, both in mouse and human subjects. Loss of HK2 in HNSCC cells resulted in reduced cell (in vitro) and tumor (in vivo) growth, as well as decreased epithelial-mesenchymal transition-mediated cell movement; in contrast, HK2-deficient HNSCC cells exhibited greater sensitivity to chemotherapeutic drugs cisplatin and 5-fluorouracil but are more resistant to photodynamic therapy, indicating that HK2 expression could selectively define treatment sensitivity in HNSCC cells. At the molecular level, it was found that HK2 alteration drove metabolic reprogramming toward OxPhos and modulated oncogenic Akt and mutant TP53-mediated signals in HNSCC cells. In summary, the present study showed that HK2 suppression could lessen HNSCC oncogenicity and modulate therapeutic sensitivity, thereby being an ideal therapeutic target for HNSCCs.
Keywords: Head and neck cancer
Hexokinase 2
Cellular malignancy
Metabolic shift
Therapeutic efficacy
Publisher: Frontiers Research Foundation
Journal: Frontiers in oncology 
EISSN: 2234-943X
DOI: 10.3389/fonc.2020.00176
Rights: Copyright © 2020 Li, Huang, Hsieh, Chen, Cheng, Chen, Liu, Chen, Huang, Lo and Chang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) ( The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
The following publication Li W-C, Huang C-H, Hsieh Y-T, Chen T-Y, Cheng L-H, Chen C-Y, Liu C-J, Chen H-M, Huang C-L, Lo J-F and Chang K-W (2020) Regulatory Role of Hexokinase 2 in Modulating Head and Neck Tumorigenesis. Front. Oncol. 10:176 is available at
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