title: High TrkB expression levels are associated with poor prognosis and EMT induction in colorectal cancer cells.
abstract: BACKGROUND
  The neurotrophic receptor tropomyosin related kinase (TrkB) is associated with tumor progression in neuroblastoma and certain human malignancies. Recent reports indicate TrkB may participate in the epithelial-mesenchymal transition (EMT). This study investigates whether TrkB expression is associated with the clinical outcome of colorectal cancer (CRC) patients and whether TrkB induces EMT in CRC cells.
  
  
  METHODS
  TrkB and E-cadherin expression in surgical tissue samples and clinicopathological data from 102 CRC patients were analyzed by real-time polymerase chain reaction and immunohistochemistry. The biological role of TrkB in CRC was analyzed using RNA interference against TrkB in the CRC cell line SW480 to assess tumor progression and the correlation between TrkB and E-cadherin expression.
  
  
  RESULTS
  Patients with high TrkB mRNA expression in clinical samples had a significantly poorer prognosis relative to those with low TrkB levels (p = 0.03). TrkB was inversely correlated with E-cadherin at both the mRNA and protein levels. In vitro, cell proliferation (p = 0.02), migration (p < 0.001), and invasion (p < 0.001) were significantly inhibited by TrkB knockdown while the anoikis rate increased in TrkB siRNA-transfected cells compared to control siRNA. Interestingly, E-cadherin expression in TrkB siRNA-transfected cells was higher than in control cells and vimentin was lower conversely.
  
  
  CONCLUSIONS
  High TrkB expression is associated with poor prognosis in CRC patients and enhanced malignant potential in terms of proliferation, migration, invasion, and anoikis inhibition in CRC cells. These results indicate TrkB could induce EMT and play an important role in CRC progression to metastasis.
authors.affiliation: Division of Reparative Medicine, Department of Gastrointestinal and Pediatric Surgery, Institute of Life Sciences, Mie University Graduate School of Medicine, 2-174, Edobashi, Tsu, Mie 514-8507, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Fujikawa
authors.forename: Koji
authors.initials: K
authors.lastname: Tanaka
authors.forename: Yuji
authors.initials: Y
authors.lastname: Toiyama
authors.forename: Susumu
authors.initials: S
authors.lastname: Saigusa
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Inoue
authors.forename: Keiichi
authors.initials: K
authors.lastname: Uchida
authors.forename: Masato
authors.initials: M
authors.lastname: Kusunoki
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology; D000368:Aged; D015820:Cadherins / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000235:genetics; D016133:Polymerase Chain Reaction; D011379:Prognosis; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000008:administration & dosage; D020813:Receptor, trkB / Q000235:genetics*; D014162:Transfection; D014746:Vimentin / Q000235:genetics
chemical_list: D015820:Cadherins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D014746:Vimentin; D020813:Receptor, trkB