@article{e2c82cc3b46e4d9999200fe72a593625,
title = "Poroptosis: A form of cell death depending on plasma membrane nanopores formation",
abstract = "Immunogenic cell death (ICD) in malignant cells can decrease tumor burden and activate antitumor immune response to obtain lasting antitumor immunity, leading to the elimination of distant metastases and prevention of recurrence. Here, we reveal that ppM1 peptide is capable of forming irreparable transmembrane pores on tumor cell membrane, leading to ICD which we name poroptosis. Poroptosis is directly dependent on cell membrane nanopores regardless of the upstream signaling of cell death. ppM1-induced poroptosis was characterized by the sustained release of intracellular LDH. This unique feature is distinct from other well-characterized types of acute necrosis induced by freezing-thawing (F/T) and detergents, which leads to the burst release of intracellular LDH. Our results suggested that steady transmembrane-nanopore-mediated subacute cell death played a vital role in subsequent activated immunity that transforms to an antitumor immune microenvironment. Selectively generating poroptosis in cancer cell could be a promise strategy for cancer therapy.",
keywords = "Cancer, Cell biology, Functional aspects of cell biology",
author = "Hao Li and Zihao Wang and Xiaocui Fang and Wenfeng Zeng and Yanlian Yang and Lingtao Jin and Xiuli Wei and Yan Qin and Chen Wang and Wei Liang",
note = "Funding Information: We thank Dr. Ping Li for ordering peptides. We thank Dr. Fayun Zhang for guidance on 4T1 model animal experiments. We thank Dr. Luoyang Wang for helpful advice on data analysis and plotting. We thank Dr. Junying Jia and Zifeng Zheng for helpful advice on the flow cytometry. We thank Yan Teng and Chunliu Liu for Confocal Microscopy work and Chunli Li for SEM work. We also thank Animal Research Center of Institute of Biophysics for technical assistance. This work is supported in part by the National Natural Science Foundation of China ( 21721002 to C.W., 21790394 to X.F.) and NIH / NCI ( R37 CA249305 , R01 CA256482 to L.J.). Funding Information: We thank Dr. Ping Li for ordering peptides. We thank Dr. Fayun Zhang for guidance on 4T1 model animal experiments. We thank Dr. Luoyang Wang for helpful advice on data analysis and plotting. We thank Dr. Junying Jia and Zifeng Zheng for helpful advice on the flow cytometry. We thank Yan Teng and Chunliu Liu for Confocal Microscopy work and Chunli Li for SEM work. We also thank Animal Research Center of Institute of Biophysics for technical assistance. This work is supported in part by the National Natural Science Foundation of China (21721002 to C.W. 21790394 to X.F.) and NIH/NCI (R37 CA249305, R01 CA256482 to L.J.). H.L. designed and performed the experiments and wrote the manuscript. Z.W. designed and performed the PEGs Blocking LDH release experiments, and contributed to the animal experiments. X.F. provided helpful advice on experiment design. X.W. and Y.Q. established stable 4T1-Muc1 cell line. W.Z. Y.Y. and L.J. provided helpful advice on manuscript writing and revision. C.W. and W.L. designed the experiments and supervised the study. This work has been included in patent applications in Chinese (201,910,388,587.0 and 202,111,270,073.9) by National Center for Nanoscience and Technology, Chinese Academy of Sciences. Publisher Copyright: {\textcopyright} 2022 The Author(s)",
year = "2022",
month = jun,
day = "17",
doi = "10.1016/j.isci.2022.104481",
language = "English (US)",
volume = "25",
journal = "iScience",
issn = "2589-0042",
publisher = "Elsevier Inc.",
number = "6",
}