Overview of tissue kallikrein and kallikrein-related peptidases in breast cancer

Abstract

The kallikrein family comprises tissue kallikrein and 14 kallikrein-related peptidases (KLKs) recognized as a subgroup of secreted trypsin- or chymotrypsin-like serine proteases. KLKs are expressed in many cellular types where they regulate important physiological activities such as semen liquefaction, immune response, neural development, blood pressure, skin desquamation and tooth enamel formation. Tissue kallikrein, the oldest member and kinin-releasing enzyme, and KLK3/PSA, a tumor biomarker for prostate cancer are the most prominent components of the family. Additionally, other KLKs have shown an abnormal expression in neoplasia, particularly in breast cancer. Thus, increased levels of some KLKs may increase extracellular matrix degradation, invasion and metastasis; other KLKs modulate cell growth, survival and angiogenesis. On the contrary, KLKs can also inhibit angiogenesis and produce tumor suppression. However, there is a lack of knowledge on how KLKs are regulated in tumor microenvironment by molecules present at the site, namely cytokines, inflammatory mediators and growth factors. Little is known about the signaling pathways that control expression/secretion of KLKs in breast cancer, and further how activation of PAR receptors may contribute to functional activity in neoplasia. A better understanding of these molecular events will allow us to consider KLKs as relevant therapeutic targets for breast cancer.

Identification of potential biomarkers and pivotal biological pathways for prostate cancer using bioinformatics analysis methods

“…Expressed and secreted by glandular epithelia of many organs including skin, mammary gland, prostate, colon, pancreas and brain, KLKs are a sort of serine proteases existed in the body fluids excreted by the above organs such as sweat, milk, and seminal fluid, involving in various physiological functions like electrolyte balance, extracellular matrix remodeling, and prohormone processing (Borgono, Michael & Diamandis, 2004; Shaw & Diamandis, 2007). Aberrant expression of KLKs can be found in several kinds of malignancies including ovarian cancer (Loessner et al, 2018), breast cancer (Figueroa et al, 2018), gastrointestinal cancer (Kontos et al, 2013), and PCa (Mavridis, Avgeris & Scorilas, 2014; McDonald & Parsons, 2016). Further on, it was suggested that KLKs could lead to proliferation of the epithelium via protease-activated receptors, which might contribute to PCa development (Ramsay et al, 2008).…”

Development of Chemical Tools to Monitor Human Kallikrein 13 (KLK13) Activity

“…Similar approaches with cathepsin-specific ABPs allowed for the detailed description of CatB, L and S trafficking and activation in cell-based models of thyroid epithelium [33]. Most importantly, the availability of cathepsin-specific activity-based probes allowed for the analysis of their activity in the tumor environment in vivo [34], an exciting perspective, given the long-postulated role of kallikreins in the tumor progression, development and metastasis [35,36]. Herein, we have presented the first tool allowing for similar analysis of the kallikrein-related peptidase 13.…”

Peer Review #1 of "Identification of potential biomarkers and pivotal biological pathways for prostate cancer using bioinformatics analysis methods (v0.1)"

“…The lipid biosynthesis is essential for membrane formation and cell signaling; for instance, the metabolic intermediates of de novo lipogenesis can serve as second messengers and regulate PCa migration and invasion (Ferro et al 2017) Manuscript to be reviewed skin, mammary gland, prostate, colon, pancreas and brain, KLKs are a sort of serine proteases existed in the body fluids excreted by the above organs such as sweat, milk, and seminal fluid, involving in various physiological functions like electrolyte balance, extracellular matrix remodeling, and prohormone processing (Borgono et al 2004;Shaw & Diamandis 2007). Aberrant expression of KLKs can be found in several kinds of malignancies including ovarian cancer (Loessner et al 2018), breast cancer (Figueroa et al 2018), gastrointestinal cancer (Kontos et al 2013), and prostate cancer (Mavridis et al 2014;McDonald & Parsons 2016). Further on, it was suggested that KLKs could lead to proliferation of the epithelium via protease-activated receptors (PARs), which might contribute to PCa development (Ramsay et al 2008).…”