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

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.

Gene Expression-Based Predication of RNA Pseudouridine Modification in Tumor Microenvironment and Prognosis of Glioma Patients

“…Tumor cells may promote the inflammatory status by releasing a wide range of cytokines ( Coussens and Werb, 2002 ; Sharma and Kanneganti, 2021 ). Chronic inflammation at the local and/or systemic level contributes to tumor pathobiology, progression, metastasis and drug resistance by reprogramming tumor cells and reorganizing the tumor immune microenvironment ( Faria et al, 2021 ). Up-regulation of CASP4 and S100A11 may contribute to the inflammatory status in the tumor immune microenvironment for the proliferation, differentiation and survival of tumor cells.…”

Molecular Characteristics, Clinical Implication, and Cancer Immunity Interactions of Pyroptosis-Related Genes in Breast Cancer

“…Immunotherapies show remarkable efficacy in treating breast cancer. Nevertheless, therapeutic effects are still limited ( 29 ). Pyroptosis offers an opportunity for alleviating immunosuppression as well as promoting an immune response in treating breast cancer ( 30 ).…”

A novel pyroptosis-related signature predicts prognosis and response to treatment in breast carcinoma

“…Research on the relationship between BC and pyroptosis is also gradually increasing. Recent studies have shown that NLRP3 inflammasome-mediated cell death occurs in BC [10]. The tumor suppressor DRD2 has been shown to trigger pyroptosis in BC [11].…”