title: Cathepsin K modulates invasion, migration and adhesion of oral squamous cell carcinomas in vitro.
abstract: OBJECTIVE
  Cathepsin K was initially discovered as an osteoclast-specific cysteine proteinase, but the enzyme is also expressed in various cancers including oral squamous cell carcinomas. This study aimed to clarify the function of cathepsin K in oral squamous cell carcinomas.
  
  
  METHODS
  Expression levels of cathepsin K were examined in six types of cell carcinomas. Carcinomas overexpressing cathepsin K were constructed. Effects of cathepsin K overexpression and treatment with odanacatib, a specific cathepsin K inhibitor, on cell invasion, migration and adhesion were analysed.
  
  
  RESULTS
  Different levels of cathepsin K were expressed in carcinomas. Cathepsin K was predominantly localised in lysosomes. Cathepsin K overexpression impaired the proliferation of carcinomas. Invasion analysis showed that cathepsin K overexpression enhanced invasion and migration of carcinomas, whereas inhibition of cathepsin K by odanacatib caused the opposite effects in carcinomas. Cathepsin K overexpression also increased cell adhesion and slightly increased surface expression of the adhesion receptor CD29/integrin β1.
  
  
  CONCLUSIONS
  The enhanced invasion of carcinomas resulting from cathepsin K overexpression is probably due to the increased cell migration and adhesion. Thus, cathepsin K is implicated not only in protein degradation but also in invasion, migration and adhesion of oral squamous cell carcinomas.
authors.affiliation: Department of Dental Pharmacology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.|Department of Clinical Oral Oncology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Yamashita
authors.affiliation: Department of Dental Pharmacology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Iwatake
authors.affiliation: Department of Dental Pharmacology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Okamoto
authors.affiliation: Department of Dentistry and Oral Surgery, Shinshu University School of Medicine, Matsumoto, Japan.
authors.forename: S-I
authors.initials: SI
authors.lastname: Yamada
authors.affiliation: Department of Clinical Oral Oncology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Umeda
authors.affiliation: Department of Dental Pharmacology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors.forename: T
authors.identifier: http://orcid.org/0000-0003-3322-1339
authors.initials: T
authors.lastname: Tsukuba
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology*; D056657:Cathepsin K / Q000378:metabolism*; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002465:Cell Movement; D006801:Humans; D009062:Mouth Neoplasms / Q000378:metabolism* / Q000473:pathology*; D009361:Neoplasm Invasiveness; D015854:Up-Regulation
chemical_list: D014408:Biomarkers, Tumor; C534130:CTSK protein, human; D056657:Cathepsin K
keywords: cathepsin K; invasion; oral squamous cell carcinoma