Gasdermin D in Different Subcellular Locations Predicts Diverse Progression, Immune Microenvironment and Prognosis in Colorectal Cancer

Wang, Jiahui; Kang, Yixin; Li, Yuxuan; Sun, Liang; Zhang, Jun; Qian, Suhui; Luo, Ke; Jiang, Yi; Sun, Lichao; Xu, Fangying

doi:10.2147/jir.s338584

Cited by 16 publications

(12 citation statements)

References 30 publications

(42 reference statements)

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“…This disagreement may be due to forced GSDMD overexpression, which can reverse gastric cancer cell proliferation by inactivating the ERK, STAT3, and PI3K/AKT pathways, and then inhibiting the Cyclin A2/CDK-2 complex to arrest the S/G2 phase transition ( Wang et al, 2018 ). Wang et al (2021) stated that GSDMD may play a dual role in carcinogenesis; GSDMD can be broken in the central linker region by caspase-1/4/11, resulting in a GSDMD N-terminal fragment (NT) and a GSDMD C-terminal fragment (NT) (CT). GSDMD-NT is a transmembrane protein that helps cells and organelles create transmembrane holes (such as mitochondrial or nuclear membrane).…”

Section: Discussionmentioning

confidence: 99%

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Gasdermin D: A potential mediator and prognostic marker of bladder cancer

El-Gamal

Abdelrahim²,

El‐Sherbiny³

et al. 2022

Front. Mol. Biosci.

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Background: Bladder cancer is considered one of the commonest widespread cancers, its presentation ranges from non-muscle invasive form to being muscle-invasive. The gasdermin family of proteins consists of six proteins. Members of gasdermin family are involved in pyroptosis; which is considered as type of inflammatory apoptosis via participation of gasdermin D and inflammatory caspases.Purpose: The goal of this research was to look into the potential involvement of gasdermin D in pathogenesis of bladder cancer, In addition, to investigate its potential role as a prognostic marker of bladder cancer.Methods: Gasdermin D gene and protein expression was examined in fresh frozen 80 bladder cancer specimens (30 NMIBC, and 50 MIBC) and the matching 80 control tissue samples utilizing real-time polymerase chain reaction and western blotting. Furthermore, the immunoreactivity of gasdermin D protein was also detected by immunohistochemistry.Results: Gasdermin D gene and protein expression showed a highly significant difference between the control and the two bladder cancer groups (p < 0.001), as demonstrated by real-time PCR, western blotting and immunohistochemistry. Cox proportional hazards regression models showed that lower gasdermin D gene expression in cancer patients (≤1.58-fold), and younger age (≤53 years) were linked with a higher risk of local tumor recurrence. Moreover, higher gasdermin D gene expression (>2.18-fold), and lymph nodes’ involvement were associated with an increased mortality.Conclusion: Gasdermin D is involved in the pathogenesis of bladder cancer and muscle invasion, in addition, tissue gasdermin D expression may be used as useful tool to predict local tumor recurrence.

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Section: Discussionmentioning

confidence: 99%

“…Organelle membrane GSDMD-NT holes are also involved in pyroptosis and other processes. GSDMD-NT, for example, stimulates the generation of reactive oxygen species when it targets the mitochondrial membrane, as well as a systemic inflammatory response and tumour immune microenvironment ( Wang et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Gasdermin D: A potential mediator and prognostic marker of bladder cancer

El-Gamal

Abdelrahim²,

El‐Sherbiny³

et al. 2022

Front. Mol. Biosci.

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“…Lmo@RBC-induced GSDMC-mediated cancer cell pyroptosis promoted the secretion of IL-6, TNF-α, and IFN-γ of bone marrow-derived DC and accumulation of DC and CD8 + T cells in tumor tissues [38]. Wang et al [39] reported that membranous GSDMD expression in colorectal cancer positively correlated with CD68 + macrophages in the tumor center and CD8 + lymphocytes in the tumor invasive front. However, nuclear GSDMD was negatively related to CD68 + macrophages in the tumor invasive front and CD8 + lymphocytes in the tumor center.…”

Section: Gsdmmentioning

confidence: 99%

The role of pyroptosis in modulating the tumor immune microenvironment

Wang

2022

Biomark Res

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The tumor immune microenvironment (TIME) plays a key role in immunosuppression in cancer, which results in tumorigenesis and tumor progression, and contributes to insensitivity to chemotherapy and immunotherapy. Understanding the mechanism of TIME formation is critical for overcoming cancer. Pyroptosis exerts a dual role in modulating the TIME. In this review, we summarize the regulatory mechanisms of pyroptosis in modulating the TIME and the potential application of targeted pyroptosis therapy in the clinic. Several treatments targeting pyroptosis have been developed; however, the majority of treatments are still in preclinical studies. Only a few agents have been used in clinic, but the outcomes are unsatisfactory. More studies are necessary to determine the role of pyroptosis in cancer, and more research is required to realize the application of treatments targeting pyroptosis in the clinic.

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“…It can be seen that the expression and role of GSDMD in cancer are complex and variable. Even the subcellular localization of GSDMD affects cancer progression and immune response ( 13 ). Therefore, the idea of targeting GSDMD to induce cancer cell pyroptosis requires more careful selection and more in-depth exploration.…”

Section: Pyroptosismentioning

confidence: 99%

Regulation of dietary polyphenols on cancer cell pyroptosis and the tumor immune microenvironment

et al. 2022

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Cancer is a major public health problem that threatens human life worldwide. In recent years, immunotherapy has made great progress in both clinical and laboratory research. But the high heterogeneity and dynamics of tumors makes immunotherapy not suitable for all cancers. Dietary polyphenols have attracted researchers' attention due to their ability to induce cancer cell pyroptosis and to regulate the tumor immune microenvironment (TIME). This review expounds the regulation of dietary polyphenols and their new forms on cancer cell pyroptosis and the TIME. These dietary polyphenols include curcumin (CUR), resveratrol (RES), epigallocatechin gallate (EGCG), apigenin, triptolide (TPL), kaempferol, genistein and moscatilin. New forms of dietary polyphenols refer to their synthetic analogs and nano-delivery, liposomes. Studies in the past decade are included. The result shows that dietary polyphenols induce pyroptosis in breast cancer cells, liver cancer cells, oral squamous cells, carcinoma cells, and other cancer cells through different pathways. Moreover, dietary polyphenols exhibit great potential in the TIME regulation by modulating the programmed cell death protein 1(PD-1)/programmed death-ligand 1 (PD-L1) axis, enhancing antitumor immune cells, weakening the function and activity of immunosuppressive cells, and targeting tumor-associated macrophages (TAMs) to reduce their tumor infiltration and promote their polarization toward the M1 type. Dietary polyphenols are also used with radiotherapy and chemotherapy to improve antitumor immunity and shape a beneficial TIME. In conclusion, dietary polyphenols induce cancer cell pyroptosis and regulate the TIME, providing new ideas for safer cancer cures.

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Gasdermin D in Different Subcellular Locations Predicts Diverse Progression, Immune Microenvironment and Prognosis in Colorectal Cancer

Cited by 16 publications

References 30 publications

Gasdermin D: A potential mediator and prognostic marker of bladder cancer

Gasdermin D: A potential mediator and prognostic marker of bladder cancer

The role of pyroptosis in modulating the tumor immune microenvironment

Regulation of dietary polyphenols on cancer cell pyroptosis and the tumor immune microenvironment

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