Abstract
Gasdermin proteins except DFNB59 are the executioners of pyroptotic cell death. Cleavage of a gasdermin by an active protease causes lytic cell death. Gasdermin C (GSDMC) is cleaved by caspase-8 in response to macrophage-secreted TNF-α. Upon cleavage, the GSDMC-N domain is liberated and oligomerized, followed by pore formation in the plasma membrane. GSDMC cleavage, LDH release, and plasma membrane translocation of GSDMC-N domain are the reliable markers for GSDMC-mediated cancer cell pyroptosis (CCP). Here, we describe the methods for examining GSDMC-mediated CCP.
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References
Cookson BT, Brennan MA (2001) Pro-inflammatory programmed cell death. Trends Microbiol 9(3):113–114
Fink SL, Cookson BT (2006) Caspase-1-dependent pore formation during pyroptosis leads to osmotic lysis of infected host macrophages. Cell Microbiol 8(11):1812–1825
Jorgensen I, Miao EA (2015) Pyroptotic cell death defends against intracellular pathogens. Immunol Rev 265(1):130–142
Friedlander AM (1986) Macrophages are sensitive to anthrax lethal toxin through an acid-dependent process. J Biol Chem 261(16):7123–7126
Ding J, Wang K, Liu W et al (2016) Pore-forming activity and structural autoinhibition of the gasdermin family. Nature 535(7610):111–116
Shi J, Zhao Y, Wang K et al (2015) Cleavage of GSDMD by inflammatory caspases determines pyroptotic cell death. Nature 526(7575):660–665
Kayagaki N, Stowe IB, Lee BL et al (2015) Caspase-11 cleaves gasdermin D for non-canonical inflammasome signalling. Nature 526(7575):666–671
Wang Y, Gao W, Shi X et al (2017) Chemotherapy drugs induce pyroptosis through caspase-3 cleavage of a gasdermin. Nature 547(7661):99–103
Hou J, Hsu JM, Hung MC (2021) Molecular mechanisms and functions of pyroptosis in inflammation and antitumor immunity. Mol Cell 81(22):4579–4590
Hou J, Zhao R, Xia W et al (2020) PD-L1-mediated gasdermin C expression switches apoptosis to pyroptosis in cancer cells and facilitates tumour necrosis. Nat Cell Biol 22(10):1264–1275
Zhang JY, Zhou B, Sun RY et al (2021) The metabolite alpha-KG induces GSDMC-dependent pyroptosis through death receptor 6-activated caspase-8. Cell Res 31(9):980–997
Xi RH, Montague J, Lin XL et al (2021) Up-regulation of gasdermin C in mouse small intestine is associated with lytic cell death in enterocytes in worm-induced type 2 immunity. Proc Natl Acad Sci USA 118(30):e2026307118
Acknowledgments
This work was funded by the Ministry of Science and Technology of Taiwan (MOST 110-2639-B-039-001-ASP to M.-C. H), Cancer Center Support Grant (NCI NIH P30 CA016672 to M.-C. H.), and a grant from the National Natural Science Foundation of China (82173107).
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Hou, J., Wang, S., Miao, R., Zhang, X., Hung, MC. (2023). Detection of Gasdermin C-Mediated Cancer Cell Pyroptosis. In: Fink, S.L. (eds) Pyroptosis. Methods in Molecular Biology, vol 2641. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-3040-2_11
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DOI: https://doi.org/10.1007/978-1-0716-3040-2_11
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