The kallikrein-related peptidase family: Dysregulation and functions during cancer progression.
Cancer is the second leading cause of death with 14 million new cases and 8.2 million cancer-related deaths worldwide in 2012. Despite the progress made in cancer therapies, neoplastic diseases are still a major therapeutic challenge notably because of intra- and inter-malignant tumour heterogeneity and adaptation/escape of malignant cells to/from treatment. New targeted therapies need to be developed to improve our medical arsenal and counter-act cancer progression. Human kallikrein-related peptidases (KLKs) are secreted serine peptidases which are aberrantly expressed in many cancers and have great potential in developing targeted therapies. The potential of KLKs as cancer biomarkers is well established since the demonstration of the association between KLK3/PSA (prostate specific antigen) levels and prostate cancer progression. In addition, a constantly increasing number of in vitro and in vivo studies demonstrate the functional involvement of KLKs in cancer-related processes. These peptidases are now considered key players in the regulation of cancer cell growth, migration, invasion, chemo-resistance, and importantly, in mediating interactions between cancer cells and other cell populations found in the tumour microenvironment to facilitate cancer progression. These functional roles of KLKs in a cancer context further highlight their potential in designing new anti-cancer approaches. In this review, we comprehensively review the biochemical features of KLKs, their functional roles in carcinogenesis, followed by the latest developments and the successful utility of KLK-based therapeutics in counteracting cancer progression.
Australian Prostate Cancer Research Centre Queensland, Translational Research Institute, 37 Kent Street, Woolloongabba, QLD 4102, Brisbane, Australia; Institute of Health and Biomedical Innovation, Translational Research Institute, Queensland University of Technology, Brisbane, Australia.
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Kryza
Institute of Health and Biomedical Innovation, Translational Research Institute, Queensland University of Technology, Brisbane, Australia.
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Silva
Institute of Health and Biomedical Innovation, Translational Research Institute, Queensland University of Technology, Brisbane, Australia.
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Loessner
Centre d'étude des pathologies respiratoires, 37032 Tours, France; Université François-Rabelais de Tours, 37032 Tours, France; INSERM, UMR 1100, 37032 Tours, France.
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Heuzé-Vourc'h
Australian Prostate Cancer Research Centre Queensland, Translational Research Institute, 37 Kent Street, Woolloongabba, QLD 4102, Brisbane, Australia; Institute of Health and Biomedical Innovation, Translational Research Institute, Queensland University of Technology, Brisbane, Australia. Electronic address: j.clements@qut.edu.au.
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Clements
D000970:Antineoplastic Agents / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D018450:Disease Progression; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007610:Kallikreins / Q000235:genetics / Q000378:metabolism*; D009369:Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics; D010447:Peptide Hydrolases / Q000235:genetics / Q000378:metabolism*; D059016:Tumor Microenvironment / Q000187:drug effects / Q000235:genetics
D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D010447:Peptide Hydrolases; D007610:Kallikreins
Cancer; Carcinogenesis; Function; KLK; Kallikrein-related peptidase; Protease