Role of the NLRP3 Inflammasome: Insights Into Cancer Hallmarks

Abstract

In response to a variety of stresses, mammalian cells activate the inflammasome for targeted caspase-dependent pyroptosis. The research community has recently begun to deduce that the activation of inflammasome is instigated by several known oncogenic stresses and metabolic perturbations; nevertheless, the role of inflammasomes in the context of cancer biology is less understood. In manipulating the expression of inflammasome, researchers have found that NLRP3 serves as a deterministic player in conducting tumor fate decisions. Understanding the mechanistic underpinning of pro-tumorigenic and anti-tumorigenic pathways might elucidate novel therapeutic onco-targets, thereby providing new opportunities to manipulate inflammasome in augmenting the anti-tumorigenic activity to prevent tumor expansion and achieve metastatic control. Accordingly, this review aims to decode the complexity of NLRP3, whereby summarizing and clustering findings into cancer hallmarks and tissue contexts may expedite consensus and underscore the potential of the inflammasome in drug translation.

Natriuretic Peptides Regulate Prostate Cells Inflammatory Behavior: Potential Novel Anticancer Agents for Prostate Cancer

“…It has been shown that the inflammasome receptor NLRP3 recognizes a diverse set of pro-inflammatory stimuli including metabolites that are actively secreted in an extracellular microenvironment during cancer expansion. These include ATP, which can activate NLRP3 inflammasome via the purinergic P2 × 7 receptors and, specifically in prostate tissue, uric acid, crystals, and infections, which have all been involved in prostate cancer progression [19].…”

“…In this context, inflammasome seem to play a crucial role. Its activation has been indeed connected to all the hallmarks of cancer [19]. For example, NLRP3 inflammasome activation in tumor cells supports a chronic inflammatory microenvironment, which promotes malignant transformation and suppress local immunity [19].…”

“…Inflammatory response represents a key event in PCa development and progression. Inflammasomes are central players in inflammation and their inappropriate activation has been implicated in many forms of cancer [19].…”

“…Upon activation, the inflammasome platform assemblies and leads to caspase-1 activation, which, in turn, is responsible for the maturation of inflammatory cytokines, including IL-1β and IL-18. Inflammasome inappropriate activation, creating a pro-inflammatory microenvironment and suppressing local immunity, appears as an emerging player in mediating cancer initiation, progression, and metastasis [18,19].…”

“…NOD-like receptor protein 3 (NLRP3) is the best characterized inflammasome receptor, and its inappropriate activation has been correlated with the development and progression of gastrointestinal, skin, breast, and hepatocellular cancer [20] and to the progression of late-stage melanoma [13]. The clinical relevance of NLRP3-inflammasome in multiple forms of cancer highlights its therapeutic promise as a molecular target [19].…”