@article{80621100f2d8436fb0259dced45822ef,
title = "PD-L1-mediated gasdermin C expression switches apoptosis to pyroptosis in cancer cells and facilitates tumour necrosis",
abstract = "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.",
author = "Junwei Hou and Rongce Zhao and Weiya Xia and Chang, {Chiung Wen} and Yun You and Hsu, {Jung Mao} and Lei Nie and Yeh Chen and Wang, {Yu Chuan} and Chunxiao Liu and Wang, {Wei Jan} and Yun Wu and Baozhen Ke and Hsu, {Jennifer L.} and Kebin Huang and Zu Ye and Yi Yang and Xianghou Xia and Yintao Li and Li, {Chia Wei} and Bin Shao and Tainer, {John A.} and Hung, {Mien Chie}",
note = "Funding Information: We thank K. Dunner Jr. and acknowledge the National Institutes of Health Cancer Center (Support grant no. P30CA016672) for supporting the High Resolution Electron Microscopy Facility at The University of Texas MD Anderson Cancer Center for the electron microscopy analysis. This work was funded in part by the National Institutes of Health (grant nos P30CA016672 and R01 AI116722 (to M.-C.H.)); a National Breast Cancer Foundation Breast Cancer Research Foundation grant to M.-C.H.; the Patel Memorial Breast Cancer Endowment Fund; the Sister Institution Network Fund for collaboration between The University of Texas MD Anderson Cancer Center and China Medical University (to M.-C.H.); the YingTsai Young Scholar Award (grant no. CMU108-YTY02 to J.-M.H.); China Medical Univesity Start Up Fund (grant no. CMU108-N-02 to W.-J.W.); the NIH (grant nos R35 CA220430 and PO1 CA092584); the Cancer Prevention and Research Institute of Texas (grant no. RP180813); Robert A. Welch Chemistry Chair (to J.A.T.); and Drug Development Center, Ministry of Education, Taiwan (grant no. 108-2311-B-241-001 to M.-C.H. and Y.C.). Publisher Copyright: {\textcopyright} 2020, The Author(s), under exclusive licence to Springer Nature Limited.",
year = "2020",
month = oct,
day = "1",
doi = "10.1038/s41556-020-0575-z",
language = "English (US)",
volume = "22",
pages = "1264--1275",
journal = "Nature cell biology",
issn = "1465-7392",
publisher = "Nature Publishing Group",
number = "10",
}