The kallikrein-related peptidase family: dysregulation and functions during cancer progression

T. Kryza, M. L. Silva, D. Loessner, N. Heuzé-Vourc'h, J. A. Clements

Research output: Contribution to journalReview ArticleOtherpeer-review

50 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)283-299
Number of pages17
JournalBiochimie
Volume122
DOIs
Publication statusPublished - Mar 2016
Externally publishedYes

Keywords

  • Cancer
  • Carcinogenesis
  • Function
  • Kallikrein-related peptidase
  • KLK
  • Protease

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