Role of Pyroptosis in Inflammation and Cancer

Overview

Journal Cell Mol Immunol

Date 2022 Aug 15

PMID 35970871

Authors

Xiang Wei

Feng Xie

Xiaoxue Zhou

Yuchen Wu

Haiyan Yan

Ting Liu

Jun Huang

Fangwei Wang

Fangfang Zhou

Long Zhang

Affiliations

Soon will be listed here.

Abstract

Pyroptosis is a form of programmed cell death mediated by gasdermin and is a product of continuous cell expansion until the cytomembrane ruptures, resulting in the release of cellular contents that can activate strong inflammatory and immune responses. Pyroptosis, an innate immune response, can be triggered by the activation of inflammasomes by various influencing factors. Activation of these inflammasomes can induce the maturation of caspase-1 or caspase-4/5/11, both of which cleave gasdermin D to release its N-terminal domain, which can bind membrane lipids and perforate the cell membrane. Here, we review the latest advancements in research on the mechanisms of pyroptosis, newly discovered influencing factors, antitumoral properties, and applications in various diseases. Moreover, this review also provides updates on potential targeted therapies for inflammation and cancers, methods for clinical prevention, and finally challenges and future directions in the field.

Citing Articles

Old drugs, new challenges: reassigning drugs for cancer therapies.

Czechowicz P, Wiech-Walow A, Slawski J, Collawn J, Bartoszewski R Cell Mol Biol Lett. 2025; 30(1):27.

PMID: 40038587 PMC: 11881393. DOI: 10.1186/s11658-025-00710-0.

Harnessing ferroptosis for precision oncology: challenges and prospects.

Fernandez-Acosta R, Vintea I, Koeken I, Hassannia B, Vanden Berghe T BMC Biol. 2025; 23(1):57.

PMID: 39988655 PMC: 11849278. DOI: 10.1186/s12915-025-02154-6.

Dietary Zinc activates the Nrf2 signaling pathway to inhibit pyroptosis and attenuate the lung inflammatory response in COPD.

Huang Y, Liang T, Liu J, Yu H, Li J, Han L Cytotechnology. 2025; 77(2):62.

PMID: 39980839 PMC: 11836256. DOI: 10.1007/s10616-025-00725-7.

Competing endogenous RNA networks in ovarian cancer: from bench to bedside.

Derogar R, Nejadi Orang F, Shadbad M EXCLI J. 2025; 24:86-112.

PMID: 39967908 PMC: 11830916. DOI: 10.17179/excli2024-7827.

Mitochondrial alterations and signatures in hepatocellular carcinoma.

Chen T, Lin S, Lee M, Wang H, Tsai K, Chou C Cancer Metastasis Rev. 2025; 44(1):34.

PMID: 39966277 PMC: 11836208. DOI: 10.1007/s10555-025-10251-9.

References

Okondo M, Rao S, Taabazuing C, Chui A, Poplawski S, Johnson D . Inhibition of Dpp8/9 Activates the Nlrp1b Inflammasome. Cell Chem Biol. 2018; 25(3):262-267.e5. PMC: 5856610. DOI: 10.1016/j.chembiol.2017.12.013. View

Li C, Qiu J, Xue Y . Low-dose Diosbulbin-B (DB) activates tumor-intrinsic PD-L1/NLRP3 signaling pathway mediated pyroptotic cell death to increase cisplatin-sensitivity in gastric cancer (GC). Cell Biosci. 2021; 11(1):38. PMC: 7881658. DOI: 10.1186/s13578-021-00548-x. View

Ruhl S, Shkarina K, Demarco B, Heilig R, Santos J, Broz P . ESCRT-dependent membrane repair negatively regulates pyroptosis downstream of GSDMD activation. Science. 2018; 362(6417):956-960. DOI: 10.1126/science.aar7607. View

Deng B, Jiao B, Liu Y, Li Y, Wang G . BIX-01294 enhanced chemotherapy effect in gastric cancer by inducing GSDME-mediated pyroptosis. Cell Biol Int. 2020; 44(9):1890-1899. PMC: 7496303. DOI: 10.1002/cbin.11395. View

Taabazuing C, Okondo M, Bachovchin D . Pyroptosis and Apoptosis Pathways Engage in Bidirectional Crosstalk in Monocytes and Macrophages. Cell Chem Biol. 2017; 24(4):507-514.e4. PMC: 5467448. DOI: 10.1016/j.chembiol.2017.03.009. View

Yan H, Luo B, Wu X, Guan F, Yu X, Zhao L . Cisplatin Induces Pyroptosis via Activation of MEG3/NLRP3/caspase-1/GSDMD Pathway in Triple-Negative Breast Cancer. Int J Biol Sci. 2021; 17(10):2606-2621. PMC: 8315016. DOI: 10.7150/ijbs.60292. View

Johnson D, Taabazuing C, Okondo M, Chui A, Rao S, Brown F . DPP8/DPP9 inhibitor-induced pyroptosis for treatment of acute myeloid leukemia. Nat Med. 2018; 24(8):1151-1156. PMC: 6082709. DOI: 10.1038/s41591-018-0082-y. View

Ewen C, Kane K, Bleackley R . A quarter century of granzymes. Cell Death Differ. 2011; 19(1):28-35. PMC: 3252830. DOI: 10.1038/cdd.2011.153. View

Cookson B, Brennan M . Pro-inflammatory programmed cell death. Trends Microbiol. 2001; 9(3):113-4. DOI: 10.1016/s0966-842x(00)01936-3. View

10.

Masters S, Dunne A, Subramanian S, Hull R, Tannahill G, Sharp F . Activation of the NLRP3 inflammasome by islet amyloid polypeptide provides a mechanism for enhanced IL-1β in type 2 diabetes. Nat Immunol. 2010; 11(10):897-904. PMC: 3103663. DOI: 10.1038/ni.1935. View

11.

Carrillo D, Chandrasekaran R, Nilsson M, Cornvik T, Liew C, Tan S . Structure of human Rack1 protein at a resolution of 2.45 Å. Acta Crystallogr Sect F Struct Biol Cryst Commun. 2012; 68(Pt 8):867-72. PMC: 3412762. DOI: 10.1107/S1744309112027480. View

12.

Sundblad V, Morosi L, Geffner J, Rabinovich G . Galectin-1: A Jack-of-All-Trades in the Resolution of Acute and Chronic Inflammation. J Immunol. 2017; 199(11):3721-3730. DOI: 10.4049/jimmunol.1701172. View

13.

Jiang S, Zhou Z, Sun Y, Zhang T, Sun L . Coral gasdermin triggers pyroptosis. Sci Immunol. 2020; 5(54). DOI: 10.1126/sciimmunol.abd2591. View

14.

Henne W, Buchkovich N, Emr S . The ESCRT pathway. Dev Cell. 2011; 21(1):77-91. DOI: 10.1016/j.devcel.2011.05.015. View

15.

Frank D, Vince J . Pyroptosis versus necroptosis: similarities, differences, and crosstalk. Cell Death Differ. 2018; 26(1):99-114. PMC: 6294779. DOI: 10.1038/s41418-018-0212-6. View

16.

Broz P, Pelegrin P, Shao F . The gasdermins, a protein family executing cell death and inflammation. Nat Rev Immunol. 2019; 20(3):143-157. DOI: 10.1038/s41577-019-0228-2. View

17.

Xia X, Wang X, Cheng Z, Qin W, Lei L, Jiang J . The role of pyroptosis in cancer: pro-cancer or pro-"host"?. Cell Death Dis. 2019; 10(9):650. PMC: 6733901. DOI: 10.1038/s41419-019-1883-8. View

18.

Zhang F, Wu L, Qian J, Qu B, Xia S, La T . Identification of the long noncoding RNA NEAT1 as a novel inflammatory regulator acting through MAPK pathway in human lupus. J Autoimmun. 2016; 75:96-104. DOI: 10.1016/j.jaut.2016.07.012. View

19.

Wree A, Eguchi A, McGeough M, Pena C, Johnson C, Canbay A . NLRP3 inflammasome activation results in hepatocyte pyroptosis, liver inflammation, and fibrosis in mice. Hepatology. 2013; 59(3):898-910. PMC: 4008151. DOI: 10.1002/hep.26592. View

20.

Silva Costa Franco M, Marim F, Alves-Silva J, Cerqueira D, Rungue M, Tavares I . AIM2 senses Brucella abortus DNA in dendritic cells to induce IL-1β secretion, pyroptosis and resistance to bacterial infection in mice. Microbes Infect. 2018; 21(2):85-93. PMC: 6430705. DOI: 10.1016/j.micinf.2018.09.001. View