GSDME mediates caspase-3-dependent pyroptosis in gastric cancer

Wang, Yubin; Yin, Bo; Li, Dinuo; Wang, Guijun; Han, Xiangdong; Sun, Xuejun

doi:10.1016/j.bbrc.2017.11.156

Cited by 243 publications

(211 citation statements)

References 27 publications

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“…In 2017, Rogers et al found that GSDME is specifically cleaved by caspase3 to generate its N-terminal fragment (GSDME-N), perforating plasma membrane to induce pyroptosis [29]. In response to chemotherapy drugs, caspase3 cleavage of GSDME drives pyroptosis in GSDME-expressing cells, including normal human primary cells (such as epidermal keratinocytes, placental epithelial cells and umbilical artery smooth muscle cells) and certain cancer cells (such as neuroblastoma, skin melanoma and gastric cancer cells) [21,30,48]. GSDME-negative cells display typical apoptotic death, and GSDME−/− mice are also protected from tissues injuries upon chemotherapy [30].…”

Section: Mechanism Of Gsdme Activationmentioning

confidence: 99%

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Mechanisms and Therapeutic Regulation of Pyroptosis in Inflammatory Diseases and Cancer

Zheng

2020

IJMS

146

111

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Programmed Cell Death (PCD) is considered to be a pathological form of cell death when mediated by an intracellular program and it balances cell death with survival of normal cells. Pyroptosis, a type of PCD, is induced by the inflammatory caspase cleavage of gasdermin D (GSDMD) and apoptotic caspase cleavage of gasdermin E (GSDME). This review aims to summarize the latest molecular mechanisms about pyroptosis mediated by pore-forming GSDMD and GSDME proteins that permeabilize plasma and mitochondrial membrane activating pyroptosis and apoptosis. We also discuss the potentiality of pyroptosis as a therapeutic target in human diseases. Blockade of pyroptosis by compounds can treat inflammatory disease and pyroptosis activation contributes to cancer therapy.

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Section: Mechanism Of Gsdme Activationmentioning

confidence: 99%

“…It is worth noting that apoptosis and pyroptosis can be distinguished by their unique morphological differences and physiological functions [29,48]. However, the underlying mechanisms are complex [53,54].…”

Section: The Association Of Pyroptosis and Apoptosismentioning

confidence: 99%

Mechanisms and Therapeutic Regulation of Pyroptosis in Inflammatory Diseases and Cancer

Zheng

2020

IJMS

146

111

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“…Additionally, GSDME functions as a tumor suppressor by potentiating pyroptosis in response to chemotherapeutics that activate caspase-3 and becomes silenced in many tumors. Cancer cells that express high levels of GSDME undergo pyroptosis in response to chemotherapies that generally result in apoptosis (Rogers et al 2017;Wang et al 2018). Further research into the regulation of GSDME expression and activation will elucidate the complex circuitry underlying its cross talk among multiple cell death pathways.…”

Section: Gsdme Activation By Caspase-3mentioning

confidence: 99%

Mechanism and Regulation of Gasdermin-Mediated Cell Death

Xia

Hollingsworth

2019

Cold Spring Harb Perspect Biol

121

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The innate immune system senses and responds to pathogens and endogenous damage through supramolecular protein complexes known as inflammasomes. Cytosolic inflammasome sensor proteins trigger inflammasome assembly on detection of infection and danger. Assembled inflammasomes activate a cascade of inflammatory caspases, which process procytokines and gasdermin D (GSDMD). Cleaved GSDMD forms membrane pores that lead to cytokine release and/or programmed lytic cell death, called pyroptosis. In this review, we provide a primer on pyroptosis and focus on its executioner, the GSDM protein family. In addition to inflammasome-mediated GSDMD pore formation, we describe recently discovered GSDMD activation by caspase-8 and elastase in Yersinia-infected macrophages and aging neutrophils, respectively, and GSDME activation by apoptotic caspases. Finally, we discuss strategies that host cells and pathogens use to restrict GSDMD pore formation, in addition to therapeutics targeting the GSDM family.

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“…Recent studies have revealed the roles of pyroptosis in several types of cancers, including colon cancer, gastric cancer, lung cancer, breast cancer, liver cancer, and glioma. However, no studies have focused on the pyroptosis in PDAC (18)(19)(20)(21)(22)(23).…”

Section: Introductionmentioning

confidence: 99%

MST1 Suppresses Pancreatic Cancer Progression via ROS-Induced Pyroptosis

Cui

Zhou

Yang

et al. 2019

Molecular Cancer Research

108

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Pancreatic ductal adenocarcinoma (PDAC) is a deadly disease, and its incidence is increasing annually. It is critical to reveal and delineate the molecular mechanism promoting PDAC development and progression. Mammalian STE20-like kinase 1 (MST1) is a proapoptotic cytoplasmic kinase and also one of the core components of the Hippo pathway. Here, we showed that MST1 expression was decreased in PDAC, and restored expression of MST1 promoted PDAC cell death and suppressed the proliferation, migration, invasion, and cell spheroid formation of PDAC via caspase-1-induced pyroptosis. Further studies demonstrated that pyroptosis induced by MST1 was independent of the Hippo pathway, but mediated by reactive oxygen species (ROS). And ROS scavenger N-acetyl-cysteine attenuated the activation of caspase-1 induced by MST1 and the effect of MST1 in PDAC cell death, proliferation, migration, and invasion. Collectively, our study demonstrated that MST1 suppressed the progression of PDAC cells at least partly through ROS-induced pyroptosis.Implications: In this study, we identified a new mechanism of MST1 in inhibiting PDAC development and progression and revealed that MST1 would be a potential prognostic and therapeutic target for PDAC.

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GSDME mediates caspase-3-dependent pyroptosis in gastric cancer

Cited by 243 publications

References 27 publications

Mechanisms and Therapeutic Regulation of Pyroptosis in Inflammatory Diseases and Cancer

Mechanisms and Therapeutic Regulation of Pyroptosis in Inflammatory Diseases and Cancer

Mechanism and Regulation of Gasdermin-Mediated Cell Death

MST1 Suppresses Pancreatic Cancer Progression via ROS-Induced Pyroptosis

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