Complexity of cancer protease biology: Cathepsin K expression and function in cancer progression

Proteases, including lysosomal cathepsins, are functionally involved in many processes in cancer progression from its initiation to invasion and metastatic spread. Only recently, cathepsin K (CatK), the cysteine protease originally reported as a collagenolytic protease produced by osteoclasts, appeared to be overexpressed as well in various types of cancers. In this review, the physiological functions of CatK are presented and compared to its potential role in pathobiolology of processes associated with tumour growth, invasion and metastasis of cancer cells and their interactions with the tumour microenvironment. CatK activity is either indirectly affecting signalling pathways, or directly degrading extracellular matrix (ECM) proteins, for example in bone metastases. Recently, CatK was also found in glioma, possibly regulating cancer stem-like cell mobilisation and modulating recently found physiological CatK substrates, including chemokines and growth factors. Moreover, CatK may be useful in differential diagnosis and may have prognostic value. Finally, the application of CatK inhibitors, which are already in clinical trials for treatment of osteoporosis, has a potential to attenuate cancer aggressiveness.