Role of the NLRP3 inflammasome in cancer

Abstract

Inflammasomes are large intracellular multi-protein signalling complexes that are formed in the cytosolic compartment as an inflammatory immune response to endogenous danger signals. The formation of the inflammasome enables activation of an inflammatory protease caspase-1, pyroptosis initiation with the subsequent cleaving of the pro-inflammatory cytokines interleukin (IL)-1β and proIL-18 to produce active forms. The inflammasome complex consists of a Nod-like receptor (NLR), the adapter apoptosis-associated speck-like (ASC) protein, and Caspase-1. Dysregulation of NLRP3 inflammasome activation is involved tumor pathogenesis, although its role in cancer development and progression remains controversial due to the inconsistent findings described. In this review, we summarize the current knowledge on the contribution of the NLRP3 inflammasome on potential cancer promotion and therapy.

Keywords: Apoptosis-associated speck-like protein; Caspase-1; Interleukin-1β; Nod-like receptor protein 3.

Fig. 1

Schematic diagram of NLR gene family

Fig. 2

Activation and signaling of NLRP3 inflammasome. BTK(Bruton’s tyrosine kinase), CaMKII (Calcium/calmodulin-dependent protein kinase II), DAMPs(damage associated molecular patterns), DHX33(DEAH-box helicase 33), ER(endoplasmic reticulum), IL(Interleukin), JAK1(Janus family of protein tyrosine kinases), LPS(Lipopolysaccharide), MCU(mitochondrial Ca 2+ uniporter), Nuclear factor-κB (NF-κB), NLRP3(NLR family, pyrin domain containing 3), NOD(nucleotide-binding and oligomerization), PAMPs(pathogen associated molecular patterns), PKR(protein kinase R), SHP(small heterodimer partner (SHP), TNF (tumor necrosis factor), Trim33(Tripartite motif-containing protein 33), VDAC1/2(voltage-dependent anion-selective channel 1/2)