Cathepsins: Potent regulators in carcinogenesis

Pharmacol Ther. 2019 Jun:198:1-19. doi: 10.1016/j.pharmthera.2019.02.003. Epub 2019 Feb 11.

Abstract

Cathepsins (CTS) are mainly lysosomal acid hydrolases extensively involved in the prognosis of different diseases, and having a distinct role in tumor progression by regulating cell proliferation, autophagy, angiogenesis, invasion, and metastasis. As all these processes conjunctively lead to cancer progression, their site-specific regulation might be beneficial for cancer treatment. CTS regulate activation of the proteolytic cascade and protein turnover, while extracellular CTS is involved in promoting extracellular matrix degradation and angiogenesis, thereby stimulating invasion and metastasis. Despite cancer regulation, the involvement of CTS in cellular adaptation toward chemotherapy and radiotherapy augments their therapeutic potential. However, lysosomal permeabilization mediated cytosolic translocation of CTS induces programmed cell death. This complex behavior of CTS generates the need to discuss the different aspects of CTS associated with cancer regulation. In this review, we mainly focused on the significance of each cathepsin in cancer signaling and their targeting which would provide noteworthy information in the context of cancer biology and therapeutics.

Keywords: Angiogenesis; Cancer; Cathepsins; Metastasis: Drug resistance: Inhibitors.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • Carcinogenesis / metabolism*
  • Cathepsins / antagonists & inhibitors
  • Cathepsins / metabolism*
  • Humans
  • Neoplasms / drug therapy
  • Neoplasms / metabolism*

Substances

  • Antineoplastic Agents
  • Cathepsins