title: Hexokinase 2 in colorectal cancer: a potent prognostic factor associated with glycolysis, proliferation and migration.
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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Surgery, Tohoku University Graduate School of Medicine, Sendai, Japan.|Department of Pathology, Tohoku University Hospital, Sendai, Japan.
authors.forename: Munetoshi
authors.initials: M
authors.lastname: Katagiri
authors.affiliation: Department of Surgery, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Karasawa
authors.affiliation: Departments of Pathology and Histotechnology, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Takagi
authors.affiliation: Department of Surgery, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Shun
authors.initials: S
authors.lastname: Nakayama
authors.affiliation: Department of Surgery, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Yabuuchi
authors.affiliation: Department of Pathology, Tohoku University Hospital, Sendai, Japan.
authors.forename: Fumiyoshi
authors.initials: F
authors.lastname: Fujishima
authors.affiliation: Department of Surgery, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Naitoh
authors.affiliation: Department of Pathology, Tohoku University Hospital, Sendai, Japan.
authors.forename: Mika
authors.initials: M
authors.lastname: Watanabe
authors.affiliation: Departments of Pathology and Histotechnology, Tohoku University Graduate School of Medicine, Sendai, Japan. t-suzuki@patholo2.med.tohoku.ac.jp.
authors.forename: Takashi
authors.initials: T
authors.lastname: Suzuki
authors.affiliation: Department of Surgery, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Michiaki
authors.initials: M
authors.lastname: Unno
authors.affiliation: Department of Pathology, Tohoku University Hospital, Sendai, Japan.|Department of Anatomic Pathology, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Hironobu
authors.initials: H
authors.lastname: Sasano
mesh_terms: D000230:Adenocarcinoma / Q000201:enzymology / Q000401:mortality / Q000473:pathology*; D000328:Adult; D000368:Aged; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation / Q000502:physiology; D015179:Colorectal Neoplasms / Q000201:enzymology / Q000401:mortality / Q000473:pathology*; D005260:Female; D055785:Gene Knockdown Techniques; D006019:Glycolysis / Q000502:physiology; D006593:Hexokinase / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016016:Proportional Hazards Models; D060888:Real-Time Polymerase Chain Reaction
chemical_list: C000609700:HK2 protein, human; D006593:Hexokinase