The DOI matches its Crossref record; 55 of the 55 references it cites were found in a registry or an index.
PD-L1-mediated gasdermin C expression switches apoptosis to pyroptosis in cancer cells and facilitates tumour necrosis
Open accessAbstract
Although pyroptosis is critical for macrophages against pathogen infection, its role and mechanism in cancer cells remains unclear. PD-L1 has been detected in the nucleus, with unknown function. Here we show that PD-L1 switches TNFα-induced apoptosis to pyroptosis in cancer cells, resulting in tumour necrosis. Under hypoxia, p-Stat3 physically interacts with PD-L1 and facilitates its nuclear translocation, enhancing the transcription of the gasdermin C (GSDMC) gene. GSDMC is specifically cleaved by caspase-8 with TNFα treatment, generating a GSDMC N-terminal domain that forms pores on the cell membrane and induces pyroptosis. Nuclear PD-L1, caspase-8 and GSDMC are required for macrophage-derived TNFα-induced tumour necrosis in vivo. Moreover, high expression of GSDMC correlates with poor survival. Antibiotic chemotherapy drugs induce pyroptosis in breast cancer. These findings identify a non-immune checkpoint function of PD-L1 and provide an unexpected concept that GSDMC/caspase-8 mediates a non-canonical pyroptosis pathway in cancer cells, causing tumour necrosis. Hou et al. show that following hypoxia PD-L1 translocates into the nucleus to enhance transcription of GSDMC, which is then cleaved and activated by caspase-8 to cause pyroptosis in cancer cells.
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Cites
Immunity, Inflammation, and Cancer
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Cited by
Pyroptosis: Mechanisms and Diseases
Yu, P., Zhang, X., Liu, N., Tang, L., Peng, C., & Chen, X. (2021) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-021-00507-5 · Cited by 2,353
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Self-citationRole of pyroptosis in inflammation and cancer
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Self-citationHypoxia signaling in human health and diseases: implications and prospects for therapeutics
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Self-citationNecroptosis and tumor progression
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Metadata
- Authors
- Hou, J., Zhao, R., Xia, W., Chang, C.-W., You, Y., Hsu, J.-M., Nie, L., Chen, Y., Wang, Y.-C., Liu, C., Wang, W.-J., Wu, Y., Ke, B., Hsu, J. L., Huang, K., Ye, Z., Yang, Y., Xia, X., Li, Y., Li, C.-W., Shao, B., Tainer, J. A., & Hung, M.-C.
- Venue
- Nature Cell Biology
- Published
- 2020-09-14
- Volume
- 22
- Issue
- 10
- Pages
- 1264-1275
- ISSN
- 1465-7392 (ISSN-L)
- 1476-4679
- OpenAlex
- W3084494759
- Cited by
- 962
- References
- 55
- FWCI
- 38.93
- Type
- journal article
- Language
- en
- Open access
- green
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- Hou, J., Zhao, R., Xia, W., Chang, C.-W., You, Y., Hsu, J.-M., Nie, L., Chen, Y., Wang, Y.-C., Liu, C., Wang, W.-J., Wu, Y., Ke, B., Hsu, J. L., Huang, K., Ye, Z., Yang, Y., Xia, X., Li, Y., . . . Hung, M.-C. (2020). PD-L1-mediated gasdermin C expression switches apoptosis to pyroptosis in cancer cells and facilitates tumour necrosis. Nature Cell Biology. https://doi.org/10.1038/s41556-020-0575-z
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
