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

и другие.

Cell Research, Год журнала: 2021, Номер 31(9), С. 980 - 997

Опубликована: Май 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.

Язык: Английский

Pyroptosis: mechanisms and diseases DOI Creative Commons

Pian Yu,

Xu Zhang, Nian Liu

и другие.

Signal Transduction and Targeted Therapy, Год журнала: 2021, Номер 6(1)

Опубликована: Март 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

Язык: Английский

Процитировано

1609

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

и другие.

Cell, Год журнала: 2020, Номер 184(1), С. 149 - 168.e17

Опубликована: Ноя. 18, 2020

Язык: Английский

Процитировано

1302

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

и другие.

Journal of Hematology & Oncology, Год журнала: 2020, Номер 13(1)

Опубликована: Авг. 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

Язык: Английский

Процитировано

989

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

и другие.

Cellular and Molecular Immunology, Год журнала: 2021, Номер 18(9), С. 2114 - 2127

Опубликована: Июль 28, 2021

Язык: Английский

Процитировано

971

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

Junwei Hou,

Rongce Zhao,

Weiya Xia

и другие.

Nature Cell Biology, Год журнала: 2020, Номер 22(10), С. 1264 - 1275

Опубликована: Сен. 14, 2020

Язык: Английский

Процитировано

721

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

Weitong Gao,

Yuqin Wang, Yang Zhou

и другие.

Signal Transduction and Targeted Therapy, Год журнала: 2022, Номер 7(1)

Опубликована: Июнь 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.

Язык: Английский

Процитировано

628

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

и другие.

Nature Reviews Drug Discovery, Год журнала: 2021, Номер 20(5), С. 384 - 405

Опубликована: Март 10, 2021

Язык: Английский

Процитировано

555

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

и другие.

Journal of Hematology & Oncology, Год журнала: 2022, Номер 15(1)

Опубликована: Дек. 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.

Язык: Английский

Процитировано

507

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

Minru Liao,

Rui Qin

и другие.

Signal Transduction and Targeted Therapy, Год журнала: 2022, Номер 7(1)

Опубликована: Авг. 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.

Язык: Английский

Процитировано

506

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

и другие.

Cell Death Discovery, Год журнала: 2020, Номер 6(1)

Опубликована: Окт. 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.

Язык: Английский

Процитировано

478