Modes of Regulated Cell Death in Cancer

Cancer Discovery, Journal Year: 2021, Volume and Issue: 11(2), P. 245 - 265

Published: Jan. 18, 2021

Cell suicide pathways, termed regulated cell death (RCD), play a critical role in organismal development, homeostasis, and pathogenesis. Here, we provide an overview of key RCD modalities, namely apoptosis, entosis, necroptosis, pyroptosis, ferroptosis. We explore how various modules serve as defense mechanism against the emergence cancer well manner which they can be exploited to drive oncogenesis. Furthermore, outline current therapeutic agents that activate consider novel RCD-based strategies for tumor elimination. SIGNIFICANCE: A variety antitumor therapeutics eliminate cells by harnessing devastating potential cellular emphasizing importance battling cancer. This review supplies mechanistic perspective distinct modalities explores important tumorigenesis. discuss double-edged sword approaches aimed at selectively manipulating eradication.

Language: Английский

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Pyroptosis, metabolism, and tumor immune microenvironment

Clinical and Translational Medicine, Journal Year: 2021, Volume and Issue: 11(8)

Published: Aug. 1, 2021

Language: Английский

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Interferon regulatory factor 1 regulates PANoptosis to prevent colorectal cancer

JCI Insight, Journal Year: 2020, Volume and Issue: 5(12)

Published: June 17, 2020

Interferon regulatory factor 1 (IRF1) regulates diverse biological functions, including modulation of cellular responses involved in tumorigenesis. Genetic mutations and altered IRF1 function are associated with several cancers. Although the immunobiology cancer is emerging, IRF1-specific mechanisms regulating tumorigenesis tissue homeostasis vivo not clear. Here, we found that mice lacking were hypersusceptible to colorectal functions both myeloid epithelial compartments confer protection against AOM/DSS-induced We further also prevents a spontaneous mouse model cancer. The attenuated cell death colons Irf1–/– was due defective pyroptosis, apoptosis, necroptosis (PANoptosis). does regulate inflammation inflammasome colon. Overall, our study identified as an upstream regulator PANoptosis induce during colitis-associated

Language: Английский

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Cucurbitacin B inhibits non-small cell lung cancer in vivo and in vitro by triggering TLR4/NLRP3/GSDMD-dependent pyroptosis

Pharmacological Research, Journal Year: 2021, Volume and Issue: 170, P. 105748 - 105748

Published: July 1, 2021

Pyroptosis, a type of programmed cell death (PCD), is characterized by swelling with bubbles, and the release inflammatory cytokines. Cucurbitacin B (CuB), extracted from muskmelon pedicel, natural bioactive product that could effectively exert anti-tumor activities in lung cancer. However, exact molecular mechanisms direct targets CuB non-small cancer (NSCLC) remain to be discovered. Here, we firstly found exerted an effect via pyroptosis NSCLC cells mice models. Next, based on docking cellular thermal shift assay (CETSA), identified directly bound Toll-like receptor 4 (TLR4) activate NLRP3 inflammasome, which further caused separation N- C-terminals Gasdermin D (GSDMD) execute pyroptosis. Moreover, enhanced mitochondrial reactive oxygen species (ROS), membrane protein Tom20 accumulation, cytosolic calcium (Ca

Language: Английский

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Inflammasomes and adaptive immune responses

Nature Immunology, Journal Year: 2021, Volume and Issue: 22(4), P. 412 - 422

Published: Feb. 18, 2021

Language: Английский

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Identification of the pyroptosis‑related prognostic gene signature and the associated regulation axis in lung adenocarcinoma

Cell Death Discovery, Journal Year: 2021, Volume and Issue: 7(1)

Published: June 25, 2021

Abstract Lung adenocarcinoma (LUAD) remains the most common deadly disease and has a poor prognosis. Pyroptosis could regulate tumour cell proliferation, invasion, metastasis, thereby affecting prognosis of cancer patients. However, role pyroptosis-related genes (PRGs) in LUAD unclear. In our study, comprehensive bioinformatics analysis was performed to construct prognostic gene model ceRNA network. The correlations between PRGs tumour-immune infiltration, mutation burden, microsatellite instability were evaluated using Pearson’s correlation analysis. A total 23 upregulated or downregulated LUAD. genetic variation landscape PRG also summarised. Functional enrichment revealed that these 33 mainly involved pyroptosis, NOD-like receptor signalling pathway, Toll-like pathway. Prognosis indicated survival rate patients with low expression NLRP7, NLRP1, NLRP2, NOD1 high CASP6 expression. constructed above five predict overall medium-to-high accuracy. Significant observed immune-cell instability. network identify lncRNA KCNQ1OT1/miR-335-5p/NLRP1/NLRP7 regulatory axis conclusion, we identified signature containing (NLRP7, NOD1, CASP6) for Our results axis, which may play an important progression Further study needs be conducted verify this result.

Language: Английский

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Which cell death modality wins the contest for photodynamic therapy of cancer?

Cell Death and Disease, Journal Year: 2022, Volume and Issue: 13(5)

Published: May 13, 2022

Abstract Photodynamic therapy (PDT) was discovered more than 100 years ago. Since then, many protocols and agents for PDT have been proposed the treatment of several types cancer. Traditionally, cell death induced by categorized into three types: apoptosis, associated with autophagy, necrosis. However, discovery other regulated modalities in recent years, it has become clear that this is a rather simple understanding mechanisms action PDT. New observations revealed cancer cells exposed to can pass through various non-conventional pathways, such as paraptosis, parthanatos, mitotic catastrophe, pyroptosis, necroptosis, ferroptosis. Nowadays, immunogenic (ICD) one most promising ways eradicate tumor activation T-cell adaptive immune response induction long-term immunological memory. ICD be triggered anti-cancer methods, including In review, we critically discuss findings on Next, emphasize role contribution these PDT-induced modalities. Finally, obstacles propose areas research will help overcome challenges lead development highly effective based

Language: Английский

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Caspase 3/GSDME-dependent pyroptosis contributes to chemotherapy drug-induced nephrotoxicity

Cell Death and Disease, Journal Year: 2021, Volume and Issue: 12(2)

Published: Feb. 15, 2021

Abstract Chemotherapy drug-induced nephrotoxicity limits clinical applications for treating cancers. Pyroptosis, a newly discovered programmed cell death, was recently reported to be associated with kidney diseases. However, the role of pyroptosis in chemotherapeutic has not been fully clarified. Herein, we demonstrate that drug cisplatin or doxorubicin, induces cleavage gasdermin E (GSDME) cultured human renal tubular epithelial cells, time- and concentration-dependent manner. Morphologically, cisplatin- doxorubicin-treated cells exhibit large bubbles emerging from membrane. Furthermore, activation caspase 3, 9, is GSDME cells. Meanwhile, silencing alleviates doxorubicin-induced HK-2 by increasing viability decreasing LDH release. In addition, treatment Ac-DMLD-CMK, polypeptide targeting mouse 3-Gsdme signaling, inhibits 3 Gsdme activation, deterioration function, attenuates injury, reduces inflammatory cytokine secretion vivo. Specifically, depends on ERK JNK signaling. NAC, reactive oxygen species (ROS) inhibitor, through signaling Thus, speculate induced chemotherapy drugs mediated ROS-JNK-caspase 3-GSDME implying therapies may prove efficacious overcoming nephrotoxicity.

Language: Английский

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The Pyroptosis-Related Signature Predicts Prognosis and Indicates Immune Microenvironment Infiltration in Gastric Cancer

Frontiers in Cell and Developmental Biology, Journal Year: 2021, Volume and Issue: 9

Published: June 11, 2021

Gastric cancer (GC) is one of the leading causes cancer-related deaths and shows high levels heterogeneity. The development a specific prognostic model important if we are to improve treatment strategies. Pyroptosis can arise in response H. pylori , primary carcinogen, also chemotherapy drugs. However, evaluation GC pyroptosis insufficient. Consensus clustering by pyroptosis-related regulators was used classify 618 patients with from four GEO cohorts. Following Cox regression differentially expressed genes, our prognosis (PS-score) built LASSO-Cox analysis. TCGA-STAD cohort as validation set. ESTIMATE, CIBERSORTx, EPIC were investigate tumor microenvironment (TME). Immunotherapy cohorts blocking PD1 / PD-L1 response. subtyping based on able according different clinical traits TME. difference between two subtypes identified this study develop which named “PS-score.” PS-score could predict his/her overall survival time. A low implies greater inflammatory cell infiltration better immunotherapy blockers. Our findings provide foundation for future research targeting its immune responses immunotherapy.

Language: Английский

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Pyroptosis, a new bridge to tumor immunity

Cancer Science, Journal Year: 2021, Volume and Issue: 112(10), P. 3979 - 3994

Published: July 12, 2021

Pyroptosis refers to the process of gasdermin (GSDM)-mediated programmed cell death (PCD). Our understanding pyroptosis has expanded beyond cells and is known involve extracellular responses. Recently, there been an increasing interest in due its emerging role activating immune system. In meantime, pyroptosis-mediated therapies, which use response kill cancer cells, have also achieved notable success a clinical setting. this review, we discuss that induced by activation double-edged sword affects all stages tumorigenesis. On one hand, inflammasome-mediated release pyroptosis-produced cytokines alter microenvironment promote development tumors evading surveillance. other can collect ignite system improve efficiency tumor immunotherapies. related some checkpoints, especially death-1 (PD-1) or death- ligand 1 (PD-L1). mainly focus on our current interplay between through pyroptosis, debate their as potential therapeutic targets.

Language: Английский

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