Radiosensitivity of colorectal cancer and radiation-induced gut damages are regulated by gasdermin E

Gao, Tieren; Cui, Lin; Huang, Chongyang; Chen, Bingxia; Chen, Jiaye; Shi, Yangyang; Zhi, Fachao

doi:10.1016/j.canlet.2021.12.034

Cited by 56 publications

(42 citation statements)

References 25 publications

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“…Given the important role of NINJ1 in PMR and pyroptosis, reducing neuroinflammation by modulating NINJ may also become a potentially effective approach. Strikingly, knockout or silencing of GSDMs is an important method to attenuate pyroptosis, which has been widely used in the treatment of tumors and pulmonary inflammation ( Song et al, 2022 ; Tan G. et al, 2022 ), nevertheless, it is rarely used in SCI research and deserves further exploration. In addition, lncRNAs and EXOs are promising regulators of inflammation and pyroptosis during SCI.…”

Section: Discussionmentioning

confidence: 99%

Pyroptosis in spinal cord injury

Yin

Gong²,

Wan³

et al. 2022

Front. Cell. Neurosci.

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Spinal cord injury (SCI) often brings devastating consequences to patients and their families. Pathophysiologically, the primary insult causes irreversible damage to neurons and glial cells and initiates the secondary damage cascade, further leading to inflammation, ischemia, and cells death. In SCI, the release of various inflammatory mediators aggravates nerve injury. Pyroptosis is a new pro-inflammatory pattern of regulated cell death (RCD), mainly mediated by caspase-1 or caspase-11/4/5. Gasdermins family are pore-forming proteins known as the executor of pyroptosis and the gasdermin D (GSDMD) is best characterized. Pyroptosis occurs in multiple central nervous system (CNS) cell types, especially plays a vital role in the development of SCI. We review here the evidence for pyroptosis in SCI, and focus on the pyroptosis of different cells and the crosstalk between them. In addition, we discuss the interaction between pyroptosis and other forms of RCD in SCI. We also summarize the therapeutic strategies for pyroptosis inhibition, so as to provide novel ideas for improving outcomes following SCI.

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Section: Discussionmentioning

confidence: 99%

Pyroptosis in spinal cord injury

Yin

Gong²,

Wan³

et al. 2022

Front. Cell. Neurosci.

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“…Exogenously activated pyroptosis has been shown to trigger potent antitumor activity, including physical and chemical factors. A recent study has revealed that GSDME is required for radiation-induced pyroptosis in cancer cells via the CASP3 pathway and that its expression increases the sensitivity of radioresistant colorectal cancer cells [ 12 ]. Yang X et al showed that cold atmospheric plasma effectively induces pyroptosis in cancer cells by activating mitochondrial pathways (JNK/cytochrome c/CASP9/CASP3) and cleaving GSDME [ 55 ].…”

Section: Discussionmentioning

confidence: 99%

“…More significantly, pyroptosis has the potential to have vast implications on cancer immunogenicity [11]. It was discovered during radiotherapy and chemotherapy that different pathways activate pyroptosis in cancers [12,13]. The most relevant and prominent modalities of PCD in cancer, such as pyroptosis and ferroptosis, could serve as biomarkers for the early diagnosis and prognosis of cancer [14,15].…”

Section: Introductionmentioning

confidence: 99%

Systematic transcriptome profiling of pyroptosis related signature for predicting prognosis and immune landscape in lower grade glioma

Gong

et al. 2022

BMC Cancer

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Background Pyroptosis is a programmed cell death mediated by the gasdermin superfamily, accompanied by inflammatory and immune responses. Exogenously activated pyroptosis is still not well characterized in the tumor microenvironment. Furthermore, whether pyroptosis-related genes (PRGs) in lower-grade glioma (LGG) may be used as a biomarker remains unknown. Methods The RNA-Sequencing and clinical data of LGG patients were downloaded from publicly available databases. Bioinformatics approaches were used to analyze the relationship between PRGs and LGG patients’ prognosis, clinicopathological features, and immune status. The NMF algorithm was used to differentiate phenotypes, the LASSO regression model was used to construct prognostic signature, and GSEA was used to analyze biological functions and pathways. The expression of the signature genes was verified using qRT-PCR. In addition, the L1000FWD and CMap tools were utilized to screen potential therapeutic drugs or small molecule compounds and validate their effects in glioma cell lines using CCK-8 and colony formation assays. Results Based on PRGs, we defined two phenotypes with different prognoses. Stepwise regression analysis was carried out to identify the 3 signature genes to construct a pyroptosis-related signature. After that, samples from the training and test cohorts were incorporated into the signature and divided by the median RiskScore value (namely, Risk-H and Risk-L). The signature shows excellent predictive LGG prognostic power in the training and validation cohorts. The prognostic signature accurately stratifies patients according to prognostic differences and has predictive value for immune cell infiltration and immune checkpoint expression. Finally, the inhibitory effect of the small molecule inhibitor fedratinib on the viability and proliferation of various glioma cells was verified using cell biology-related experiments. Conclusion This study developed and validated a novel pyroptosis-related signature, which may assist instruct clinicians to predict the prognosis and immunological status of LGG patients more precisely. Fedratinib was found to be a small molecule inhibitor that significantly inhibits glioma cell viability and proliferation, which provides a new therapeutic strategy for gliomas.

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“…In conclusion, GSDME participates in the regulation of chemotherapy toxicities during chemotherapy ( Figure 3B ). In addition, a recent study has given evidence that GSDME-mediated pyroptosis is also engaged in the damaged intestine, stomach, liver and pancreas tissues caused by radiotherapy for colorectal cancer ( Tan et al, 2022 ). Given this, how to balance the role of GSDME in tumor therapy and therapeutic toxicity is a challenge to be addressed when designing anti-tumor therapy regimens targeting GSDME.…”

Section: The Role Of Gsdme In Diseasesmentioning

confidence: 99%

Gasdermin E: A Prospective Target for Therapy of Diseases

et al. 2022

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Gasdermin E (GSDME) is a member of the gasdermin protein family, which mediates programmed cell death including apoptosis and pyroptosis. Recently, it was suggested that GSDME is activated by chemotherapeutic drugs to stimulate pyroptosis of cancer cells and trigger anti-tumor immunity, which is identified as a tumor suppressor. However, GSDME-mediated pyroptosis contributes to normal tissue damage, leading to pathological inflammations. Inhibiting GSDME-mediated pyroptosis might be a potential target in ameliorating inflammatory diseases. Therefore, targeting GSDME is a promising option for the treatment of diseases in the future. In this review, we introduce the roles of GSDME-driven programmed cell death in different diseases and the potential targeted therapies of GSDME, so as to provide a foundation for future research.

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Radiosensitivity of colorectal cancer and radiation-induced gut damages are regulated by gasdermin E

Cited by 56 publications

References 25 publications

Pyroptosis in spinal cord injury

Pyroptosis in spinal cord injury

Systematic transcriptome profiling of pyroptosis related signature for predicting prognosis and immune landscape in lower grade glioma

Gasdermin E: A Prospective Target for Therapy of Diseases

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