Kallikrein-related peptidases KLK5, KLK7 and KLK14 are important proteases in skin desquamation and aberrant KLK activity is associated with inflammatory skin diseases such as Netherton syndrome but also with various serious forms of cancer.
Immunocytochemical analyses demonstrate that hepsin and TMPRSS2 colocalize on the cell surface with the secreted serine proteases KLK4 and KLK14, only in membrane protrusions, suggesting that reciprocal proteolytic interactions occur in defined cellular structures that are important during cancer dissemination for cell migration, invasion and survival.
Though KLK14 functioning in cancer is poorly understood, it has been implicated in HGF/Met signaling, given that KLK14 proteolytically inhibits HGF activator-inhibitor 1 (HAI-1), which strongly inhibits pro-HGF activators, thereby contributing to tumor progression.
Human kallikrein gene 14 (KLK14) is a recently discovered member of the tissue kallikrein family of secreted serine proteases, which includes hK3/prostate-specific antigen, the best cancer biomarker to date.