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Hexokinase 2 overexpression promotes the proliferation and survival of laryngeal squamous cell carcinoma

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Tumor Biology

Abstract

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.

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Acknowledgments

This study was supported by grants from the National Natural Science Foundation of China (No. 30801282) and the Research Fund for the Doctoral Program of Higher Education of China (No. 20020487062).

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Authors and Affiliations

  1. Department of Otorhinolaryngology, Union Hospital of Tongji Medical College, Huazhong University of Science and Technology, Number 1277 Jiefang Avenue, Wuhan, Hubei, China

    Jian Chen, Sulin Zhang, Yuncheng Li, Zhengang Tang & Weijia Kong

  2. Department of Head and Neck Surgery, Hubei Cancer Hospital, Wuhan, Hubei, China

    Jian Chen

  3. Key laboratory of Neurological Disease, Ministry of Education, Wuhan, China

    Weijia Kong

Authors
  1. Jian Chen
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  2. Sulin Zhang
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  3. Yuncheng Li
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  4. Zhengang Tang
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  5. Weijia Kong
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Corresponding authors

Correspondence to Sulin Zhang or Weijia Kong.

Additional information

J. Chen and S. Zhang contributed equally to this work.

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Chen, J., Zhang, S., Li, Y. et al. Hexokinase 2 overexpression promotes the proliferation and survival of laryngeal squamous cell carcinoma. Tumor Biol. 35, 3743–3753 (2014). https://doi.org/10.1007/s13277-013-1496-2

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  • DOI: https://doi.org/10.1007/s13277-013-1496-2

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