Cathepsin K modulates invasion, migration and adhesion of oral squamous cell carcinomas in vitro

Oral Dis. 2017 May;23(4):518-525. doi: 10.1111/odi.12643. Epub 2017 Mar 9.

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.

Materials and 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.

Keywords: cathepsin K; invasion; oral squamous cell carcinoma.

MeSH terms

  • Biomarkers, Tumor / metabolism*
  • Carcinoma, Squamous Cell / metabolism*
  • Carcinoma, Squamous Cell / pathology*
  • Cathepsin K / metabolism*
  • Cell Adhesion
  • Cell Line, Tumor
  • Cell Movement
  • Humans
  • Mouth Neoplasms / metabolism*
  • Mouth Neoplasms / pathology*
  • Neoplasm Invasiveness
  • Up-Regulation

Substances

  • Biomarkers, Tumor
  • CTSK protein, human
  • Cathepsin K