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.
Funding source: Universidad Austral de Chile
Award Identifier / Grant number: S-2015-61
Funding statement: The authors wish to thank Dirección de Investigación y Desarrollo from Universidad Austral de Chile (Grant S-2015-61 to P.E.) and Fondo de Innovacion para la Competitividad (FIC17-6) for its continuous support.
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©2018 Walter de Gruyter GmbH, Berlin/Boston
Articles in the same Issue
- Frontmatter
- Highlight: The 7th International Symposium on Kallikreins and Kallikrein-Related Peptidases
- Obituary
- Manfred Schmitt (1947–2018)
- Functional interrelationships between the kallikrein-related peptidases family and the classical kinin system in the human neutrophil
- Overview of tissue kallikrein and kallikrein-related peptidases in breast cancer
- Kallikrein-related peptidases in lung diseases
- The miRNA-kallikrein interaction: a mosaic of epigenetic regulation in cancer
- Mining human cancer datasets for kallikrein expression in cancer: the ‘KLK-CANMAP’ Shiny web tool
- Specificity profiling of human trypsin-isoenzymes
- Activation and activity of glycosylated KLKs 3, 4 and 11
- Microenvironment proteinases, proteinase-activated receptor regulation, cancer and inflammation
- Kallikrein-related peptidase 6 orchestrates astrocyte form and function through proteinase activated receptor-dependent mechanisms
- Kallikrein-related peptidase 5 and seasonal influenza viruses, limitations of the experimental models for activating proteases
- Novel splice variants of the human kallikrein-related peptidases 11 (KLK11) and 12 (KLK12), unraveled by next-generation sequencing technology
- Insights into the activity control of the kallikrein-related peptidase 6: small-molecule modulators and allosterism
- Kallikrein-related peptidase 14 is the second KLK protease targeted by the serpin vaspin
- Profiling system for skin kallikrein proteolysis applied in gene-deficient mouse models
- Evidence that cell surface localization of serine protease activity facilitates cleavage of the protease activated receptor CDCP1
- Kallikrein-related peptidase 7 overexpression in melanoma cells modulates cell adhesion leading to a malignant phenotype
- KLK5, a novel potential suppressor of vaginal carcinogenesis
Articles in the same Issue
- Frontmatter
- Highlight: The 7th International Symposium on Kallikreins and Kallikrein-Related Peptidases
- Obituary
- Manfred Schmitt (1947–2018)
- Functional interrelationships between the kallikrein-related peptidases family and the classical kinin system in the human neutrophil
- Overview of tissue kallikrein and kallikrein-related peptidases in breast cancer
- Kallikrein-related peptidases in lung diseases
- The miRNA-kallikrein interaction: a mosaic of epigenetic regulation in cancer
- Mining human cancer datasets for kallikrein expression in cancer: the ‘KLK-CANMAP’ Shiny web tool
- Specificity profiling of human trypsin-isoenzymes
- Activation and activity of glycosylated KLKs 3, 4 and 11
- Microenvironment proteinases, proteinase-activated receptor regulation, cancer and inflammation
- Kallikrein-related peptidase 6 orchestrates astrocyte form and function through proteinase activated receptor-dependent mechanisms
- Kallikrein-related peptidase 5 and seasonal influenza viruses, limitations of the experimental models for activating proteases
- Novel splice variants of the human kallikrein-related peptidases 11 (KLK11) and 12 (KLK12), unraveled by next-generation sequencing technology
- Insights into the activity control of the kallikrein-related peptidase 6: small-molecule modulators and allosterism
- Kallikrein-related peptidase 14 is the second KLK protease targeted by the serpin vaspin
- Profiling system for skin kallikrein proteolysis applied in gene-deficient mouse models
- Evidence that cell surface localization of serine protease activity facilitates cleavage of the protease activated receptor CDCP1
- Kallikrein-related peptidase 7 overexpression in melanoma cells modulates cell adhesion leading to a malignant phenotype
- KLK5, a novel potential suppressor of vaginal carcinogenesis