Pyroptosis: mechanisms and diseases

Yu, Pei; Zhang, Xu; Liu, Nian; Tang, Ling; Peng, Cong; Chen, Xiang

doi:10.1038/s41392-021-00507-5

Cited by 1,270 publications

(934 citation statements)

References 446 publications

(253 reference statements)

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“…Another important nding shows that this prognostic model is signi cantly related to the TME, con rming that pyroptosis plays a non-negligible role in the TME. More and more evidence shows that pyroptosis is particularly important for the formation of tumors and TME, especially the tumor immune microenvironment (30). Studies have con rmed that about 95% of cervical cancer patients may be caused by persistent infection with HPV, and the human immune system plays an important role in the infection response process, laying the foundation for immunotherapy of cancer (31).…”

Section: Discussionmentioning

confidence: 99%

Identification of the Pyroptosis-related Signature for Predicting Prognosis in Cervical Cancer

Zhou

Zheng

et al. 2021

Preprint

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Background: Cervical cancer (CC) is one of the most common malignancies in gynecology. There is still a lack of specific biomarkers for the diagnosis and prognosis of CC. Pyroptosis is one of the methods of programmed cell death, and its various components are related to the occurrence, invasion, and metastasis of tumors. However, the role of pyroptosis in CC has not yet been elucidated.Methods: This study focuses on the development of a prognostic signature associated with pyroptosis for CC patients using integrated bioinformatics to elucidate the relationship between the signature and the tumor microenvironment and immune response.Results: We identified a prognostic signature based on eight pyroptosis-related genes (PRGs), with better prognostic survival in the low-risk group (P<0.05) and AUC values greater than 0.7. The results of the multi-factor Cox regression analysis indicated that the signature could be used as an independent prognostic factor, and both the DCA and the Nomogram suggested that the prognostic signature had good predictive power. Interestingly, this prognostic signature can also be applied to multiple tumors. In addition, the tumor microenvironment and immune infiltration status were significantly different between high and low-risk groups (P<0. 05). The core gene GZMB was screened and the CC-associated GZMB/ miR-378a/TRIM52-AS1 regulatory axis was constructed.Conclusion: The study successfully established the prognostic signature based on eight PRGs and reflected their tumor microenvironment and immune infiltration. The GZMB/ miR-378a/TRIM52-AS1 regulatory axis may play an important regulatory role in the development of CC, and further experimental studies are needed to validate these results subsequently.

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Section: Discussionmentioning

confidence: 99%

Identification of the Pyroptosis-related Signature for Predicting Prognosis in Cervical Cancer

Zhou

Zheng

et al. 2021

Preprint

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“…Given the dual role of pyroptosis, its molecular components are, as one would expect, abnormally and differentially expressed across different cancers (Table 2 ). GSDMs, for instance, are deregulated in breast, gastric, cervical, and lung cancers, among others, and have been shown to control proliferation, metastasis, therapeutic resistance, and antitumor immunity while acting as either oncogenes or tumor suppressors [ 65 , 66 ]. In gastric cancer (GC), GSDMD expression was markedly decreased and resulted in enhanced tumor proliferation both in vitro and in vivo, possibly by accelerating S/G2 cell transition [ 57 ].…”

Section: Pyroptosis and Its Constituents In Cancermentioning

confidence: 99%

Pyroptosis at the forefront of anticancer immunity

Loveless

Bloomquist

Teng

2021

J Exp Clin Cancer Res

182

128

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Tumor resistance to apoptosis and the immunosuppressive tumor microenvironment are two major contributors to poor therapeutic responses during cancer intervention. Pyroptosis, a lytic and inflammatory programmed cell death pathway distinct from apoptosis, has subsequently sparked notable interest among cancer researchers for its potential to be clinically harnessed and to address these problems. Recent evidence indicates that pyroptosis induction in tumor cells leads to a robust inflammatory response and marked tumor regression. Underlying its antitumor effect, pyroptosis is mediated by pore-forming gasdermin proteins that facilitate immune cell activation and infiltration through their release of pro-inflammatory cytokines and immunogenic material following cell rupture. Considering its inflammatory nature, however, aberrant pyroptosis may also be implicated in the formation of a tumor supportive microenvironment, as evidenced by the upregulation of gasdermin proteins in certain cancers. In this review, the molecular pathways leading to pyroptosis are introduced, followed by an overview of the seemingly entangled links between pyroptosis and cancer. We describe what is known regarding the impact of pyroptosis on anticancer immunity and give insight into the potential of harnessing pyroptosis as a tool and applying it to novel or existing anticancer strategies.

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“…Pyroptosis is an inflammatory form of regulated cell death morphologically characterised by cell swelling and membrane perforation and molecularly by inflammosomeinduced caspase-1 mediated gasdermin-D (GSDMD) cleavage or caspase-3 mediated gasdermin-E (GSDME) cleavage [2,100]. Activation of NOD-like receptors (NLRP1, NLRP3, NLRC4) initiates pyroptotic signalling in response to bacterial infection and other stresses, in order to facilitate pathogen clearance and enhance the innate immune response [100]. In a model of lung cancer, p53 was reported to directly bind to and activate NLRP3 thus promoting pyroptosis [101].…”

Section: Immunogenicity Of Cell Deathmentioning

confidence: 99%

Dying to Survive—The p53 Paradox

Lees

Sessler

McDade

2021

Cancers

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The p53 tumour suppressor is best known for its canonical role as “guardian of the genome”, activating cell cycle arrest and DNA repair in response to DNA damage which, if irreparable or sustained, triggers activation of cell death. However, despite an enormous amount of work identifying the breadth of the gene regulatory networks activated directly and indirectly in response to p53 activation, how p53 activation results in different cell fates in response to different stress signals in homeostasis and in response to p53 activating anti-cancer treatments remains relatively poorly understood. This is likely due to the complex interaction between cell death mechanisms in which p53 has been activated, their neighbouring stressed or unstressed cells and the local stromal and immune microenvironment in which they reside. In this review, we evaluate our understanding of the burgeoning number of cell death pathways affected by p53 activation and how these may paradoxically suppress cell death to ensure tissue integrity and organismal survival. We also discuss how these functions may be advantageous to tumours that maintain wild-type p53, the understanding of which may provide novel opportunity to enhance treatment efficacy.

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Pyroptosis: mechanisms and diseases

Cited by 1,270 publications

References 446 publications

Identification of the Pyroptosis-related Signature for Predicting Prognosis in Cervical Cancer

Identification of the Pyroptosis-related Signature for Predicting Prognosis in Cervical Cancer

Pyroptosis at the forefront of anticancer immunity

Dying to Survive—The p53 Paradox

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