Cysteine cathepsins: multifunctional enzymes in cancer

Nat Rev Cancer. 2006 Oct;6(10):764-75. doi: 10.1038/nrc1949.

Abstract

Cysteine cathepsins are highly upregulated in a wide variety of cancers by mechanisms ranging from gene amplification to post-transcriptional modification. Their localization within intracellular lysosomes often changes during neoplastic progression, resulting in secretion of both inactive and active forms and association with binding partners on the tumour cell surface. Secreted, cell-surface and intracellular cysteine cathepsins function in proteolytic pathways that increase neoplastic progression. Direct proof for causal roles in tumour growth, migration, invasion, angiogenesis and metastasis has been shown by downregulating or ablating the expression of individual cysteine cathepsins in tumour cells and in transgenic mouse models of human cancer.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Cysteine Endopeptidases / metabolism*
  • Cysteine Proteinase Inhibitors / therapeutic use*
  • Humans
  • Neoplasms / drug therapy
  • Neoplasms / enzymology*
  • Neoplasms / pathology

Substances

  • Cysteine Proteinase Inhibitors
  • Cysteine Endopeptidases