Targeting the NLRP3 Inflammasome As a New Therapeutic Option for Overcoming Cancer

Overview

Journal Cancers (Basel)

Publisher MDPI

Specialty Oncology

Date 2021 Jun 2

PMID 34064909

Citations 36

Authors

Sonia Missiroli

Mariasole Perrone

Caterina Boncompagni

Chiara Borghi

Alberto Campagnaro

Francesco Marchetti

Gabriele Anania

Pantaleo Greco

Francesco Fiorica

Paolo Pinton

Carlotta Giorgi

Affiliations

Soon will be listed here.

Abstract

Inflammasomes are multiprotein complexes that regulate the maturation and secretion of the proinflammatory cytokines interleukin-1beta (IL-1β and interleukin-18 (IL-18) in response to various intracellular stimuli. As a member of the inflammasomes family, NLRP3 is the most studied and best characterized inflammasome and has been shown to be involved in several pathologies. Recent findings have made it increasingly apparent that the NLRP3 inflammasome may also play a central role in tumorigenesis, and it has attracted attention as a potential anticancer therapy target. In this review, we discuss the role of NLRP3 in the development and progression of cancer, offering a detailed summary of NLRP3 inflammasome activation (and inhibition) in the pathogenesis of various forms of cancer. Moreover, we focus on the therapeutic potential of targeting NLRP3 for cancer therapy, emphasizing how understanding NLRP3 inflammasome-dependent cancer mechanisms might guide the development of new drugs that target the inflammatory response of tumor-associated cells.

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References

Veeranki S . Role of inflammasomes and their regulators in prostate cancer initiation, progression and metastasis. Cell Mol Biol Lett. 2013; 18(3):355-67. PMC: 6275599. DOI: 10.2478/s11658-013-0095-y. View

Gurung P, Anand P, Malireddi R, Vande Walle L, Van Opdenbosch N, Dillon C . FADD and caspase-8 mediate priming and activation of the canonical and noncanonical Nlrp3 inflammasomes. J Immunol. 2014; 192(4):1835-46. PMC: 3933570. DOI: 10.4049/jimmunol.1302839. View

Segovia-Mendoza M, Morales-Montor J . Immune Tumor Microenvironment in Breast Cancer and the Participation of Estrogen and Its Receptors in Cancer Physiopathology. Front Immunol. 2019; 10:348. PMC: 6407672. DOI: 10.3389/fimmu.2019.00348. View

Liu W, Guo W, Wu J, Luo Q, Tao F, Gu Y . A novel benzo[d]imidazole derivate prevents the development of dextran sulfate sodium-induced murine experimental colitis via inhibition of NLRP3 inflammasome. Biochem Pharmacol. 2013; 85(10):1504-12. DOI: 10.1016/j.bcp.2013.03.008. View

Karan D, Tawfik O, Dubey S . Expression analysis of inflammasome sensors and implication of NLRP12 inflammasome in prostate cancer. Sci Rep. 2017; 7(1):4378. PMC: 5491527. DOI: 10.1038/s41598-017-04286-4. View

Brocker C, Kim D, Melia T, Karri K, Velenosi T, Takahashi S . Long non-coding RNA Gm15441 attenuates hepatic inflammasome activation in response to PPARA agonism and fasting. Nat Commun. 2020; 11(1):5847. PMC: 7673042. DOI: 10.1038/s41467-020-19554-7. View

Wei Q, Guo P, Mu K, Zhang Y, Zhao W, Huai W . Estrogen suppresses hepatocellular carcinoma cells through ERβ-mediated upregulation of the NLRP3 inflammasome. Lab Invest. 2015; 95(7):804-16. DOI: 10.1038/labinvest.2015.63. View

Chassaing B, Aitken J, Malleshappa M, Vijay-Kumar M . Dextran sulfate sodium (DSS)-induced colitis in mice. Curr Protoc Immunol. 2014; 104:15.25.1-15.25.14. PMC: 3980572. DOI: 10.1002/0471142735.im1525s104. View

Rossol M, Pierer M, Raulien N, Quandt D, Meusch U, Rothe K . Extracellular Ca2+ is a danger signal activating the NLRP3 inflammasome through G protein-coupled calcium sensing receptors. Nat Commun. 2012; 3:1329. PMC: 3535422. DOI: 10.1038/ncomms2339. View

10.

Okamoto M, Liu W, Luo Y, Tanaka A, Cai X, Norris D . Constitutively active inflammasome in human melanoma cells mediating autoinflammation via caspase-1 processing and secretion of interleukin-1beta. J Biol Chem. 2009; 285(9):6477-88. PMC: 2825443. DOI: 10.1074/jbc.M109.064907. View

11.

Hafner-Bratkovic I, Susjan P, Lainscek D, Tapia-Abellan A, Cerovic K, Kadunc L . NLRP3 lacking the leucine-rich repeat domain can be fully activated via the canonical inflammasome pathway. Nat Commun. 2018; 9(1):5182. PMC: 6281599. DOI: 10.1038/s41467-018-07573-4. View

12.

Soysal S, Tzankov A, Muenst S . Role of the Tumor Microenvironment in Breast Cancer. Pathobiology. 2015; 82(3-4):142-52. DOI: 10.1159/000430499. View

13.

Fujita K, Ewing C, Isaacs W, Pavlovich C . Immunomodulatory IL-18 binding protein is produced by prostate cancer cells and its levels in urine and serum correlate with tumor status. Int J Cancer. 2010; 129(2):424-32. PMC: 3040782. DOI: 10.1002/ijc.25705. View

14.

Zitvogel L, Kepp O, Galluzzi L, Kroemer G . Inflammasomes in carcinogenesis and anticancer immune responses. Nat Immunol. 2012; 13(4):343-51. DOI: 10.1038/ni.2224. View

15.

Bauer C, Duewell P, Mayer C, Lehr H, Fitzgerald K, Dauer M . Colitis induced in mice with dextran sulfate sodium (DSS) is mediated by the NLRP3 inflammasome. Gut. 2010; 59(9):1192-9. DOI: 10.1136/gut.2009.197822. View

16.

Haghshenas M, Hosseini S, Mahmoudi M, Saberi-Firozi M, Farjadian S, Ghaderi A . IL-18 serum level and IL-18 promoter gene polymorphism in Iranian patients with gastrointestinal cancers. J Gastroenterol Hepatol. 2009; 24(6):1119-22. DOI: 10.1111/j.1440-1746.2009.05791.x. View

17.

Church L, McDermott M . Canakinumab: a human anti-IL-1β monoclonal antibody for the treatment of cryopyrin-associated periodic syndromes. Expert Rev Clin Immunol. 2010; 6(6):831-41. DOI: 10.1586/eci.10.66. View

18.

Wang H, Luo Q, Feng X, Zhang R, Li J, Chen F . NLRP3 promotes tumor growth and metastasis in human oral squamous cell carcinoma. BMC Cancer. 2018; 18(1):500. PMC: 5930757. DOI: 10.1186/s12885-018-4403-9. View

19.

Wang H, Wang Y, Du Q, Lu P, Fan H, Lu J . Inflammasome-independent NLRP3 is required for epithelial-mesenchymal transition in colon cancer cells. Exp Cell Res. 2016; 342(2):184-92. DOI: 10.1016/j.yexcr.2016.03.009. View

20.

Richards M, ORegan L, Mas-Droux C, Blot J, Cheung J, Hoelder S . An autoinhibitory tyrosine motif in the cell-cycle-regulated Nek7 kinase is released through binding of Nek9. Mol Cell. 2009; 36(4):560-70. PMC: 2807034. DOI: 10.1016/j.molcel.2009.09.038. View