PMID- 32195170 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20200928 IS - 2234-943X (Print) IS - 2234-943X (Electronic) IS - 2234-943X (Linking) VI - 10 DP - 2020 TI - Regulatory Role of Hexokinase 2 in Modulating Head and Neck Tumorigenesis. PG - 176 LID - 10.3389/fonc.2020.00176 [doi] LID - 176 AB - 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. CI - Copyright (c) 2020 Li, Huang, Hsieh, Chen, Cheng, Chen, Liu, Chen, Huang, Lo and Chang. FAU - Li, Wan-Chun AU - Li WC AD - Institute of Oral Biology, School of Dentistry, National Yang-Ming University, Taipei, Taiwan. AD - Department of Dentistry, School of Dentistry, National Yang-Ming University, Taipei, Taiwan. AD - Cancer Progression Research Center, National Yang-Ming University, Taipei, Taiwan. FAU - Huang, Chien-Hsiang AU - Huang CH AD - Institute of Oral Biology, School of Dentistry, National Yang-Ming University, Taipei, Taiwan. FAU - Hsieh, Yi-Ta AU - Hsieh YT AD - Institute of Oral Biology, School of Dentistry, National Yang-Ming University, Taipei, Taiwan. FAU - Chen, Tsai-Ying AU - Chen TY AD - Institute of Oral Biology, School of Dentistry, National Yang-Ming University, Taipei, Taiwan. FAU - Cheng, Li-Hao AU - Cheng LH AD - Institute of Oral Biology, School of Dentistry, National Yang-Ming University, Taipei, Taiwan. FAU - Chen, Chang-Yi AU - Chen CY AD - Institute of Oral Biology, School of Dentistry, National Yang-Ming University, Taipei, Taiwan. FAU - Liu, Chung-Ji AU - Liu CJ AD - Institute of Oral Biology, School of Dentistry, National Yang-Ming University, Taipei, Taiwan. AD - Department of Dentistry, School of Dentistry, National Yang-Ming University, Taipei, Taiwan. AD - Department of Oral and Maxillofacial Surgery, MacKay Memorial Hospital, Taipei, Taiwan. AD - Department of Medical Research, MacKay Memorial Hospital, Taipei, Taiwan. FAU - Chen, Hsin-Ming AU - Chen HM AD - School of Dentistry and Department of Dentistry, National Taiwan University Medical College and National Taiwan University Hospital, Taipei, Taiwan. FAU - Huang, Chien-Ling AU - Huang CL AD - Department of Health Technology and Informatics (HTI), The Hong Kong Polytechnic University (PolyU), Kowloon, Hong Kong. FAU - Lo, Jeng-Fang AU - Lo JF AD - Institute of Oral Biology, School of Dentistry, National Yang-Ming University, Taipei, Taiwan. AD - Department of Dentistry, School of Dentistry, National Yang-Ming University, Taipei, Taiwan. AD - Cancer Progression Research Center, National Yang-Ming University, Taipei, Taiwan. AD - Department of Stomatology, Taipei Veterans General Hospital, Taipei, Taiwan. FAU - Chang, Kuo-Wei AU - Chang KW AD - Institute of Oral Biology, School of Dentistry, National Yang-Ming University, Taipei, Taiwan. AD - Department of Dentistry, School of Dentistry, National Yang-Ming University, Taipei, Taiwan. AD - Cancer Progression Research Center, National Yang-Ming University, Taipei, Taiwan. AD - Department of Stomatology, Taipei Veterans General Hospital, Taipei, Taiwan. LA - eng PT - Journal Article DEP - 20200303 PL - Switzerland TA - Front Oncol JT - Frontiers in oncology JID - 101568867 EIN - Front Oncol. 2020 Mar 31;10:410. PMID: 32296642 PMC - PMC7063098 OTO - NOTNLM OT - cellular malignancy OT - head and neck cancer OT - hexokinase 2 OT - metabolic shift OT - therapeutic efficacy EDAT- 2020/03/21 06:00 MHDA- 2020/03/21 06:01 PMCR- 2020/01/01 CRDT- 2020/03/21 06:00 PHST- 2019/11/26 00:00 [received] PHST- 2020/01/31 00:00 [accepted] PHST- 2020/03/21 06:00 [entrez] PHST- 2020/03/21 06:00 [pubmed] PHST- 2020/03/21 06:01 [medline] PHST- 2020/01/01 00:00 [pmc-release] AID - 10.3389/fonc.2020.00176 [doi] PST - epublish SO - Front Oncol. 2020 Mar 3;10:176. doi: 10.3389/fonc.2020.00176. eCollection 2020.