The metabolite α-KG induces GSDMC-dependent pyroptosis through death receptor 6-activated caspase-8 DOI Creative Commons
Jia-yuan Zhang, Bo Zhou,

Ru-yue Sun

et al.

Cell Research, Journal Year: 2021, Volume and Issue: 31(9), P. 980 - 997

Published: May 19, 2021

Abstract Pyroptosis is a form of regulated cell death mediated by gasdermin family members, among which the function GSDMC has not been clearly described. Herein, we demonstrate that metabolite α-ketoglutarate (α-KG) induces pyroptosis through caspase-8-mediated cleavage GSDMC. Treatment with DM-αKG, cell-permeable derivative α-KG, elevates ROS levels, leads to oxidation plasma membrane-localized receptor DR6. Oxidation DR6 triggers its endocytosis, and then recruits both pro-caspase-8 receptosome protein-protein interactions. The herein provides platform for active caspase-8, thereby leading pyroptosis. Moreover, this α-KG-induced could inhibit tumor growth metastasis in mouse models. Interestingly, efficiency α-KG inducing relies on an acidic environment reduced MDH1 converted L-2HG further boosts levels. lactic acid, end product glycolysis, builds improved facilitate more production L-2HG, makes originally pyroptosis-resistant cancer cells susceptible This study only illustrates pyroptotic pathway linked metabolites but also identifies unreported principal axis extending from ROS-initiated endocytosis potential clinical application therapy.

Language: Английский

Pyroptosis: mechanisms and diseases DOI Creative Commons

Pian Yu,

Xu Zhang, Nian Liu

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2021, Volume and Issue: 6(1)

Published: March 29, 2021

Abstract Currently, pyroptosis has received more and attention because of its association with innate immunity disease. The research scope expanded the discovery gasdermin family. A great deal evidence shows that can affect development tumors. relationship between tumors is diverse in different tissues genetic backgrounds. In this review, we provide basic knowledge pyroptosis, explain tumors, focus on significance tumor treatment. addition, further summarize possibility as a potential treatment strategy describe side effects radiotherapy chemotherapy caused by pyroptosis. brief, double-edged sword for rational use dual effect will help us explore formation ideas patients to develop new drugs based

Language: Английский

Citations

1568
Synergism of TNF-α and IFN-γ Triggers Inflammatory Cell Death, Tissue Damage, and Mortality in SARS-CoV-2 Infection and Cytokine Shock Syndromes DOI Creative Commons
Rajendra Karki, Bhesh Raj Sharma, Shraddha Tuladhar

et al.

Cell, Journal Year: 2020, Volume and Issue: 184(1), P. 149 - 168.e17

Published: Nov. 18, 2020

Language: Английский

Citations

1282
Ferroptosis, necroptosis, and pyroptosis in anticancer immunity DOI Creative Commons
Rong Tang, Jin Xu, Bo Zhang

et al.

Journal of Hematology & Oncology, Journal Year: 2020, Volume and Issue: 13(1)

Published: Aug. 10, 2020

Abstract In recent years, cancer immunotherapy based on immune checkpoint inhibitors (ICIs) has achieved considerable success in the clinic. However, ICIs are significantly limited by fact that only one third of patients with most types respond to these agents. The induction cell death mechanisms other than apoptosis gradually emerged as a new treatment strategy because tumors harbor innate resistance apoptosis. date, possibility combining two modalities not been discussed systematically. Recently, few studies revealed crosstalk between distinct and antitumor immunity. pyroptosis, ferroptosis, necroptosis combined showed synergistically enhanced activity, even ICI-resistant tumors. Immunotherapy-activated CD8+ T cells traditionally believed induce tumor via following main pathways: (i) perforin-granzyme (ii) Fas-FasL. identified mechanism which suppress growth inducing ferroptosis provoked review relationship system activation. Hence, this review, we summarize knowledge reciprocal interaction immunity mechanisms, particularly necroptosis, three potentially novel immunogenic death. Because evidence is derived from using animal models, also reviewed related bioinformatics data available for human tissues public databases, partially confirmed presence interactions activation

Language: Английский

Citations

976
NLRP3 inflammasome activation and cell death DOI Open Access
Yi Huang, Wen Xu, Rongbin Zhou

et al.

Cellular and Molecular Immunology, Journal Year: 2021, Volume and Issue: 18(9), P. 2114 - 2127

Published: July 28, 2021

Language: Английский

Citations

952
PD-L1-mediated gasdermin C expression switches apoptosis to pyroptosis in cancer cells and facilitates tumour necrosis DOI

Junwei Hou,

Rongce Zhao,

Weiya Xia

et al.

Nature Cell Biology, Journal Year: 2020, Volume and Issue: 22(10), P. 1264 - 1275

Published: Sept. 14, 2020

Language: Английский

Citations

713
Autophagy, ferroptosis, pyroptosis, and necroptosis in tumor immunotherapy DOI Creative Commons

Weitong Gao,

Yuqin Wang, Yang Zhou

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2022, Volume and Issue: 7(1)

Published: June 20, 2022

Abstract In recent years, immunotherapy represented by immune checkpoint inhibitors (ICIs) has led to unprecedented breakthroughs in cancer treatment. However, the fact that many tumors respond poorly or even not ICIs, partly caused absence of tumor-infiltrating lymphocytes (TILs), significantly limits application ICIs. Converting these “cold” into “hot” may ICIs is an unsolved question immunotherapy. Since it a general characteristic cancers resist apoptosis, induction non-apoptotic regulated cell death (RCD) emerging as new treatment strategy. Recently, several studies have revealed interaction between RCD and antitumor immunity. Specifically, autophagy, ferroptosis, pyroptosis, necroptosis exhibit synergistic responses while possibly exerting inhibitory effects on responses. Thus, targeted therapies (inducers inhibitors) against combination with exert potent activity, resistant This review summarizes multilevel relationship immunity RCD, including necroptosis, potential targeting improve efficacy malignancy.

Language: Английский

Citations

612
Channelling inflammation: gasdermins in physiology and disease DOI Open Access
Xing Liu, Shiyu Xia, Zhibin Zhang

et al.

Nature Reviews Drug Discovery, Journal Year: 2021, Volume and Issue: 20(5), P. 384 - 405

Published: March 10, 2021

Language: Английский

Citations

549
Regulated cell death (RCD) in cancer: key pathways and targeted therapies DOI Creative Commons
Peng Fu,

Minru Liao,

Rui Qin

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2022, Volume and Issue: 7(1)

Published: Aug. 13, 2022

Regulated cell death (RCD), also well-known as programmed (PCD), refers to the form of that can be regulated by a variety biomacromolecules, which is distinctive from accidental (ACD). Accumulating evidence has revealed RCD subroutines are key features tumorigenesis, may ultimately lead establishment different potential therapeutic strategies. Hitherto, targeting with pharmacological small-molecule compounds been emerging promising avenue, rapidly progressed in many types human cancers. Thus, this review, we focus on summarizing not only apoptotic and autophagy-dependent signaling pathways, but crucial pathways other subroutines, including necroptosis, pyroptosis, ferroptosis, parthanatos, entosis, NETosis lysosome-dependent (LCD) cancer. Moreover, further discuss current situation several improve cancer treatment, such single-target, dual or multiple-target compounds, drug combinations, some new strategies would together shed light future directions attack vulnerabilities drugs for purposes.

Language: Английский

Citations

499
Targeting cell death pathways for cancer therapy: recent developments in necroptosis, pyroptosis, ferroptosis, and cuproptosis research DOI Creative Commons

Xuhui Tong,

Rong Tang,

Mingming Xiao

et al.

Journal of Hematology & Oncology, Journal Year: 2022, Volume and Issue: 15(1)

Published: Dec. 8, 2022

Abstract Many types of human cells self-destruct to maintain biological homeostasis and defend the body against pathogenic substances. This process, called regulated cell death (RCD), is important for various activities, including clearance aberrant cells. Thus, RCD pathways represented by apoptosis have increased in importance as a target development cancer medications recent years. However, because tumor show avoidance apoptosis, which causes treatment resistance recurrence, numerous studies been devoted alternative mortality processes, namely necroptosis, pyroptosis, ferroptosis, cuproptosis; these modalities extensively studied shown be crucial therapy effectiveness. Furthermore, evidence suggests that undergoing may alter immunogenicity microenvironment (TME) some extent, rendering it more suitable inhibiting progression metastasis. In addition, other components TME undergo abovementioned forms induce immune attacks on cells, resulting enhanced antitumor responses. Hence, this review discusses molecular processes features cuproptosis effects novel proliferation Importantly, introduces complex affect biology. It also summarizes potential agents nanoparticles or inhibit their therapeutic based from vivo vitro reports clinical trials inducers evaluated treatments patients. Lastly, we summarized impact modulating drug advantages adding modulators over conventional treatments.

Language: Английский

Citations

490
The caspase-3/GSDME signal pathway as a switch between apoptosis and pyroptosis in cancer DOI Creative Commons
Mingxia Jiang, Ling Qi, Lisha Li

et al.

Cell Death Discovery, Journal Year: 2020, Volume and Issue: 6(1)

Published: Oct. 28, 2020

Abstract Apoptosis has long been recognized as a mechanism that kills the cancer cells by cytotoxic drugs. In recent years, studies have proved pyroptosis can also shrink tumors and inhibit proliferation. Both apoptosis are caspase-dependent programmed cell death pathways. Cysteinyl aspartate specific proteinase-3 (Caspase-3) is common key protein in pathways, when activated, expression level of tumor suppressor gene Gasdermin E (GSDME) determines death. When GSDME highly expressed, active caspase-3 cuts it releases N-terminal domain to punch holes membrane, resulting swelling, rupture, low, will lead classical death, which apoptosis. More interestingly, researchers found be located upstream caspase-3, connecting extrinsic, intrinsic apoptotic Then, promoting activation, forming self-amplifying feed-forward loop. GSDME-mediated correlated with side effects chemotherapy anti-tumor immunity. This article mainly reviews caspase-3/GSDME signal pathway switch between cancer, provide new strategies targets for treatment.

Language: Английский

Citations

471