Cathepsin K and Its Specific Target in Mediating Breast Cancer Skeletal Metastasis

Cathepsin K (CTSK), a cysteine protease predominantly seen in osteoclasts, degrades protein present in the organic matrix of bone inducing bone resorption. Based on the accumulating evidences, CTSK has an established role in osteoclast mediated bone resorption, progression of cancer invasion, migration and extracellular matrix degradation through activating several pathways, which vary from other classes of cysteine proteinases such as Cathepsin B & L. Studies in the past have shown that CTSK is a key protease in breast cancer-induced bone metastases which are found highly expressed in human breast and prostate carcinomas. However, the involvement of CTSK in breast and prostate cancer development remains unclear. Bone is a key site of breast and prostate cancer metastasis and most patients with advanced disease encounter complications from incurable bone lesions. Therefore, CTSK can be viewed as an alternative target for treating patients with metastatic bone disease. This review discusses the molecular insights into CTSK and its specific targets in mediating breast cancer skeletal metastasis, so as to find the novelty of cathepsin K therapeutic target for the treatment of patients with osteolytic bone metastases.