PMID- 24363061 OWN - NLM STAT- MEDLINE DCOM- 20140609 LR - 20220317 IS - 1423-0380 (Electronic) IS - 1010-4283 (Linking) VI - 35 IP - 4 DP - 2014 Apr TI - Hexokinase 2 overexpression promotes the proliferation and survival of laryngeal squamous cell carcinoma. PG - 3743-53 LID - 10.1007/s13277-013-1496-2 [doi] AB - Proliferating cancer cells preferentially use anaerobic glycolysis rather than oxidative phosphorylation for energy production. Hexokinase 2 (HK2) is highly expressed in many malignant cells and is necessary for anaerobic glycolysis. The role of HK2 in laryngeal squamous cell carcinoma (LSCC) is unknown. In this study, the expression of HK2 in LSCC was investigated and the effect of inhibiting HK2 expression with small hairpin RNA (shRNA) on tumor growth was investigated. Using immunohistochemistry, HK2 expression was assessed in LSCC tissues. Human laryngeal carcinoma Hep-2 cells were stably transfected with a plasmid expressing HK2 shRNA (pGenesil-1.1-HK2) and were compared to control cells with respect to the cell cycle, cell viability, apoptosis, and their ability to form xenograft tumors. HK2 expression was significantly higher in LSCC than in papilloma or glottis polypus. Tumor samples of higher T, N, and TNM stage often had stronger HK2 staining. HK2 shRNA reduced HK2 mRNA, protein levels, and HK activity in Hep-2 cells. HK2 cells expressing shRNA demonstrated a higher G0-G1 ratio, increased apoptosis, and reduced viability. Xenograft tumors derived from cells expressing HK2 shRNA were smaller and had lower proliferation than those from untransfected or control-plasmid-transfected cells. In conclusion, depletion of HK2 expression resulted in reduced xenograft tumor development likely by reducing proliferation, altering the cell cycle, reducing cell viability and activating apoptosis. These data suggest that HK2 plays an important role in the development of LSCC and represents a potential therapeutic target for LSCC. FAU - Chen, Jian AU - Chen J AD - Department of Otorhinolaryngology, Union Hospital of Tongji Medical College, Huazhong University of Science and Technology, Number 1277 Jiefang Avenue, Wuhan, Hubei, China. FAU - Zhang, Sulin AU - Zhang S FAU - Li, Yuncheng AU - Li Y FAU - Tang, Zhengang AU - Tang Z FAU - Kong, Weijia AU - Kong W LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20131221 PL - Netherlands TA - Tumour Biol JT - Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine JID - 8409922 RN - 0 (Ki-67 Antigen) RN - EC 2.7.1.1 (Hexokinase) SB - IM MH - Adult MH - Aged MH - Carcinoma, Squamous Cell/mortality/*pathology MH - Cell Line, Tumor MH - *Cell Proliferation MH - Glycolysis MH - Head and Neck Neoplasms/mortality/*pathology MH - Hexokinase/analysis/genetics/*physiology MH - Humans MH - Ki-67 Antigen/analysis MH - Laryngeal Neoplasms/etiology/mortality/*pathology MH - Middle Aged MH - Squamous Cell Carcinoma of Head and Neck MH - Xenograft Model Antitumor Assays EDAT- 2013/12/24 06:00 MHDA- 2014/06/10 06:00 CRDT- 2013/12/24 06:00 PHST- 2013/09/28 00:00 [received] PHST- 2013/11/28 00:00 [accepted] PHST- 2013/12/24 06:00 [entrez] PHST- 2013/12/24 06:00 [pubmed] PHST- 2014/06/10 06:00 [medline] AID - 10.1007/s13277-013-1496-2 [doi] PST - ppublish SO - Tumour Biol. 2014 Apr;35(4):3743-53. doi: 10.1007/s13277-013-1496-2. Epub 2013 Dec 21.