The roles of proteases in prostate cancer

Hannu Koistinen, Ruusu Maaria Kovanen, Morley D. Hollenberg, Antoine Dufour, Evette S. Radisky, Ulf Håkan Stenman, Jyotsna Batra, Judith Clements, John D. Hooper, Eleftherios Diamandis, Oliver Schilling, Antti Rannikko, Tuomas Mirtti

Research output: Contribution to journalReview articlepeer-review


Since the proposition of the pro-invasive activity of proteolytic enzymes over 70 years ago, several roles for proteases in cancer progression have been established. About half of the 473 active human proteases are expressed in the prostate and many of the most well-characterized members of this enzyme family are regulated by androgens, hormones essential for development of prostate cancer. Most notably, several kallikrein-related peptidases, including KLK3 (prostate-specific antigen, PSA), the most well-known prostate cancer marker, and type II transmembrane serine proteases, such as TMPRSS2 and matriptase, have been extensively studied and found to promote prostate cancer progression. Recent findings also suggest a critical role for proteases in the development of advanced and aggressive castration-resistant prostate cancer (CRPC). Perhaps the most intriguing evidence for this role comes from studies showing that the protease-activated transmembrane proteins, Notch and CDCP1, are associated with the development of CRPC. Here, we review the roles of proteases in prostate cancer, with a special focus on their regulation by androgens.

Original languageEnglish (US)
Pages (from-to)493-513
Number of pages21
JournalIUBMB Life
Issue number6
StatePublished - Jun 2023


  • AR
  • CDCP1
  • CUB domain-containing protein 1
  • FAP
  • KLK
  • MMP
  • Notch
  • PAR
  • androgen
  • androgen receptor
  • fibroblast activation protein
  • hepsin
  • kallikrein-related peptidases
  • matriptase
  • matrix metalloproteinase
  • peptidases
  • prostate cancer
  • protease-activated receptor
  • proteases
  • trypsin
  • uPA
  • urokinase-type plasminogen activator

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Genetics
  • Clinical Biochemistry
  • Cell Biology


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