Pyroptosis, inflammasome, and gasdermins in tumor immunity

Ouyang, Xiaohu; Zhou, Jianhua; Lin, Lan; Zhang, Zili; Luo, Shanshan; Hu, Desheng

doi:10.1177/17534259221143216

Cited by 21 publications

(17 citation statements)

References 102 publications

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“…Additionally, it has been associated with drug resistance during tumor chemotherapy [34]. The GSDMS family plays a crucial role in pyroptotic processes, with GSDMB, GSDMC, GSDMD, and GSDME mediating enhanced immune responses against certain cancers [35]. Notably, GSDMD-mediated pyroptotic response is well-documented [36].…”

Section: Discussionmentioning

confidence: 99%

GSDMS are potential therapeutic targets and prognostic biomarkers in breast cancer

Huang,

Han,

et al. 2024

Preprint

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Pyroptosis is a new type of programmed death recently discovered,the GSDM family plays a crucial role in pyroptotic processes. Numerous studies have reported that GSDM family can either inhibit or promote tumor development; However, the mechanism of action in breast cancer is unclear. In this study, we employed diverse online databases to investigate the differential expression of GSDMS in breast cancer compared to para-cancer and transcriptional variations among molecular subtypes. Furthermore, we explored the association between GSDMS and clinical characteristics, assessed its prognostic value, examined gene alterations, investigated the relationship between subtypes and RFS, evaluated immune cell infiltration level, and analyzed the level of GSDMS methylation in breast cancer. We observed a significant upregulation of GSDMD in breast cancer, while GSDMB-E and PJVK exhibited low expression levels in this malignancy. GSDMB and GSDMC were highly expressed in HER2-positive breast cancer but showed low expression in triple-negative and luminal subtypes. GSDMD, GSDME, and PJVK displayed high expression specifically in the luminal phenotype of breast cancer while being downregulated in Her2+ and triple-negative subtypes. The expression pattern of GSDMS was closely associated with distinct clinical features. Missense mutation, deletion mutation, amplification, and deep deletion primarily accounted for alterations observed in the genes encoding GSDMA-E and PJVK with change rates ranging from 0.9% to 19%. Survival analysis revealed that elevated expressions of both GSDMD and PJVK were correlated with improved prognosis among breast cancer patients. Furthermore, the members of the GSDM family demonstrated strong associations with immune-infiltrating cells within the of breast cancer. DNA methylation analysis indicated lower levels along with decreased methylation patterns for GSDMC, GSDMD, and PJVK in breast cancer tissues; conversely increased methylation was observed for both GSDMA and GSDME. Our study systematically elucidates the expression and prognostic significance of GSDMS in breast cancer, as well as the potential prognostic implications of GSDMD and PJVK in breast cancer. These findings provide valuable guidance for clinicians regarding drug utilization.

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Section: Discussionmentioning

confidence: 99%

GSDMS are potential therapeutic targets and prognostic biomarkers in breast cancer

Huang,

Han,

et al. 2024

Preprint

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“…[34,35] Gasdermin (GSDM) pore GSDM proteins have been identi ed as a key executioner of pyroptosis. [36,37] Gasdermin D (GSDMD) forms pores in the plasma membrane, which leads to cytokine release from cells and in ammatory cell death. [38] However, GSDMD is also highly expressed in the mitochondrial membrane, where it induces the release of ROS and causes mitochondrial damage.…”

Section: Mitochondrial Permeability Transition Pore and Voltagedepend...mentioning

confidence: 99%

Role of mitochondrial dysfunction in kidney disease: Insights from the cGAS-STING signaling pathway

Li,

Liu,

Feng

et al. 2024

Chinese Medical Journal

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Over the past decade, mitochondrial dysfunction has been investigated as a key contributor to acute and chronic kidney disease. However, the precise molecular mechanisms linking mitochondrial damage to kidney disease remain elusive. The recent insights into the cyclic guanosine monophosphate-adenosine monophosphate (GMP-AMP) synthetase (cGAS)-stimulator of interferon gene (STING) signaling pathway have revealed its involvement in many renal diseases. One of these findings is that mitochondrial DNA (mtDNA) induces inflammatory responses via the cGAS-STING pathway. Herein, we provide an overview of the mechanisms underlying mtDNA release following mitochondrial damage, focusing specifically on the association between mtDNA release-activated cGAS-STING signaling and the development of kidney diseases. Furthermore, we summarize the latest findings of cGAS-STING signaling pathway in cell, with a particular emphasis on its downstream signaling related to kidney diseases. This review intends to enhance our understanding of the intricate relationship among the cGAS-STING pathway, kidney diseases, and mitochondrial dysfunction.

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“…The GSDM proteins are predominantly expressed in the epithelium of the esophagus, stomach, colon, bladder, vagina, and prostate ( 29 , 55 ). Their presence in different tumors varies significantly, contributing to distinct roles within these tumors ( 56 , 57 ) ( Table 1 ).…”

Section: The Expression Of Gsdm and Clinical Significance In Tumor Im...mentioning

confidence: 99%

Gasdermins: a dual role in pyroptosis and tumor immunity

Yang,

Jiang

2024

Front. Immunol.

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The gasdermin (GSDM) protein family plays a pivotal role in pyroptosis, a process critical to the body’s immune response, particularly in combatting bacterial infections, impeding tumor invasion, and contributing to the pathogenesis of various inflammatory diseases. These proteins are adept at activating inflammasome signaling pathways, recruiting immune effector cells, creating an inflammatory immune microenvironment, and initiating pyroptosis. This article serves as an introduction to the GSDM protein-mediated pyroptosis signaling pathways, providing an overview of GSDMs’ involvement in tumor immunity. Additionally, we explore the potential applications of GSDMs in both innovative and established antitumor strategies.

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Pyroptosis, inflammasome, and gasdermins in tumor immunity

Cited by 21 publications

References 102 publications

GSDMS are potential therapeutic targets and prognostic biomarkers in breast cancer

GSDMS are potential therapeutic targets and prognostic biomarkers in breast cancer

Role of mitochondrial dysfunction in kidney disease: Insights from the cGAS-STING signaling pathway

Gasdermins: a dual role in pyroptosis and tumor immunity

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