Hexokinase 2 in colorectal cancer: A potent prognostic factor associated with glycolysis, proliferation and migration

Munetoshi Katagiri, Hideaki Karasawa, Kiyoshi Takagi, Shun Nakayama, Shinichi Yabuuchi, Fumiyoshi Fujishima, Takeshi Naitoh, Mika Watanabe, Takashi Suzuki, Michiaki Unno, Hironobu Sasano

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Background. It is well known that proliferating carcinoma cells preferentially use aerobic glycolysis rather than oxidative phosphorylation for energy production. Hexokinase 2 (HK2) plays a pivotal role in the glycolytic pathway. Previous studies have demonstrated that HK2 activity is markedly increased in various malignant neoplasms, but the clinical and biological significance of HK2 remain largely unclear in the colorectal carcinoma. Patients and methods. We performed immunohistochemistry for HK2 in 195 colorectal carcinoma tissues. We also used HCT8 and HT29 colon carcinoma cells in in vitro studies. Results. HK2 immunoreactivity was detected in 100 out of 195 (51%) colorectal carcinoma tissues, and the immunohistochemical HK2 status was significantly associated with tumor size, depth of invasion, liver metastasis and TNM stage in these cases. Moreover, the HK2 status was significantly associated with increased incidence of recurrence and overall mortality of the patients, and multivariate analyses demonstrated that HK2 status was an independent prognostic factor for both disease-free and overall survival. Subsequent in vitro experiments revealed that both HCT8 and HT29 colon carcinoma cells transfected with specific siRNA for HK2 significantly decreased the lactate production, proliferation activity and migration property. Conclusion. These results suggest that HK2 plays important roles in the glycolytic, proliferation and migration properties of colorectal carcinoma and, therefore, HK2 status is a potent worse prognostic factor in colorectal cancer patients.

Original languageEnglish
Pages (from-to)351-360
Number of pages10
JournalHistology and Histopathology
Volume32
Issue number4
DOIs
Publication statusPublished - 2017 Apr

Keywords

  • Colorectal cancer
  • Immunohistochemistry
  • Invasion
  • Prognosis
  • Proliferation

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Histology

Fingerprint Dive into the research topics of 'Hexokinase 2 in colorectal cancer: A potent prognostic factor associated with glycolysis, proliferation and migration'. Together they form a unique fingerprint.

  • Cite this