NLRP3 inflammasome-mediated cytokine production and pyroptosis cell death in breast cancer

J Biomed Sci. 2021 Apr 12;28(1):26. doi: 10.1186/s12929-021-00724-8.

Abstract

Breast cancer is the most diagnosed malignancy in women. Increasing evidence has highlighted the importance of chronic inflammation at the local and/or systemic level in breast cancer pathobiology, influencing its progression, metastatic potential and therapeutic outcome by altering the tumor immune microenvironment. These processes are mediated by a variety of cytokines, chemokines and growth factors that exert their biological functions either locally or distantly. Inflammasomes are protein signaling complexes that form in response to damage- and pathogen-associated molecular patterns (DAMPS and PAMPS), triggering the release of pro-inflammatory cytokines. The dysregulation of inflammasome activation can lead to the development of inflammatory diseases, neurodegeneration, and cancer. A crucial signaling pathway leading to acute and chronic inflammation occurs through the activation of NLRP3 inflammasome followed by caspase 1-dependent release of IL-1β and IL-18 pro-inflammatory cytokines, as well as, by gasdermin D-mediated pyroptotic cell death. In this review we focus on the role of NLRP3 inflammasome and its components in breast cancer signaling, highlighting that a more detailed understanding of the clinical relevance of these pathways could significantly contribute to the development of novel therapeutic strategies for breast cancer.

Keywords: Breast cancer; Gasdermins; IL-1β; NLRP3 inflammasome.

Publication types

  • Review

MeSH terms

  • Animals
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / physiopathology
  • Cytokines / metabolism*
  • Female
  • Humans
  • Inflammasomes / genetics*
  • Inflammasomes / metabolism
  • Mice
  • NLR Family, Pyrin Domain-Containing 3 Protein / genetics*
  • NLR Family, Pyrin Domain-Containing 3 Protein / metabolism
  • Pyroptosis / physiology*

Substances

  • Cytokines
  • Inflammasomes
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • NLRP3 protein, human