title: Overexpression of PBK/TOPK Contributes to Tumor Development and Poor Outcome of Esophageal Squamous Cell Carcinoma.
abstract: PDZ-binding kinase/T-cell-originated protein kinase (PBK/TOPK) is a serine-threonine kinase and overexpressed in various types of cancer. PBK/TOPK is associated with tumor cell development and progression through suppression of p53 function. In this study, we tested whether PBK acts as a cancer-promoting factor by being overexpressed in esophageal squamous cell carcinoma (ESCC).
  
  
  
  We analyzed PBK/TOPK expression in 15 ESCC cell lines, and 54 primary ESCC tumors that were curatively resected between 1994 and 2007.
  
  
  
  Overexpression of the PBK/TOPK protein was detected in 93% (14/15) ESCC cell lines and 19% (10/54) primary ESCC tumor samples, and significantly correlated with macroscopic appearance and tumor depth. PBK/TOPK positivity was independently associated with worse outcome in multivariate analysis (p=0.0235, hazard ratio=3.58). Knockdown of PBK/TOPK using specific siRNAs inhibited the cell proliferation, invasion/migration of PBK/TOPK-overexpressing ESCC cell lines.
  
  
  
  These findings suggest that PBK/TOPK plays a crucial role in tumor malignant potential through its overexpression in ESCC.
authors.affiliation: Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kawaramachihirokoji, Kyoto, Japan.
authors.forename: Takuma
authors.initials: T
authors.lastname: Ohashi
authors.affiliation: Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kawaramachihirokoji, Kyoto, Japan skomatsu@koto.kpu-m.ac.jp.
authors.forename: Shuhei
authors.initials: S
authors.lastname: Komatsu
authors.affiliation: Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kawaramachihirokoji, Kyoto, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Ichikawa
authors.affiliation: Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kawaramachihirokoji, Kyoto, Japan.
authors.forename: Mahito
authors.initials: M
authors.lastname: Miyamae
authors.affiliation: Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kawaramachihirokoji, Kyoto, Japan.
authors.forename: Wataru
authors.initials: W
authors.lastname: Okajima
authors.affiliation: Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kawaramachihirokoji, Kyoto, Japan.
authors.forename: Taisuke
authors.initials: T
authors.lastname: Imamura
authors.affiliation: Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kawaramachihirokoji, Kyoto, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Kiuchi
authors.affiliation: Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kawaramachihirokoji, Kyoto, Japan.
authors.forename: Keiji
authors.initials: K
authors.lastname: Nishibeppu
authors.affiliation: Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kawaramachihirokoji, Kyoto, Japan.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Kosuga
authors.affiliation: Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kawaramachihirokoji, Kyoto, Japan.
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Konishi
authors.affiliation: Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kawaramachihirokoji, Kyoto, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Shiozaki
authors.affiliation: Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kawaramachihirokoji, Kyoto, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Fujiwara
authors.affiliation: Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kawaramachihirokoji, Kyoto, Japan.
authors.forename: Kazuma
authors.initials: K
authors.lastname: Okamoto
authors.affiliation: Department of Pathology, National Cancer Center Hospital, Tokyo, Japan.|Department of Basic Pathology, National Defense Medical College, Tokorozawa, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Tsuda
authors.affiliation: Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kawaramachihirokoji, Kyoto, Japan.
authors.forename: Eigo
authors.initials: E
authors.lastname: Otsuji
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology*; D002453:Cell Cycle; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004938:Esophageal Neoplasms / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism*
chemical_list: D020929:Mitogen-Activated Protein Kinase Kinases; C409022:PDZ-binding kinase
keywords: PBK/TOPK; esophageal squamous cell carcinoma; oncogene; prognosis