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Induction of Pyroptosis and Its Implications in Cancer Management.

ABSTRACT: Pyroptosis is a gasdermins mediated programmed cell death, which has been widely studied in inflammatory disease models. Recently, there are growing evidences that pyroptosis can be chemically induced in cancer cells without any bacterial or viral infection. Pyroptosis may affect all stages of carcinogenesis and has become a new topic in cancer research. In this review, we first briefly introduced pyroptosis. In the subsequent section, we discussed the induction of pyroptosis in cancer and its potential role as a promising target for cancer therapy. In addition, the biological characteristics of gasdermin D (GSDMD) and gasdermin E (GSDME), two important pyroptosis substrates, and their prognostic role in cancer management were reviewed. These results help us to understand the pathogenesis of cancer and develop new drugs, which based on pyroptosis modulation, for cancer patients.

SUBMITTER: Wang YY

PROVIDER: S-EPMC6775187 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Induction of Pyroptosis and Its Implications in Cancer Management.

Wang Yan-Yang YY Liu Xin-Lan XL Zhao Ren R

Frontiers in oncology 20190926

Pyroptosis is a gasdermins mediated programmed cell death, which has been widely studied in inflammatory disease models. Recently, there are growing evidences that pyroptosis can be chemically induced in cancer cells without any bacterial or viral infection. Pyroptosis may affect all stages of carcinogenesis and has become a new topic in cancer research. In this review, we first briefly introduced pyroptosis. In the subsequent section, we discussed the induction of pyroptosis in cancer and its p ...[more]

PMID: 31616642

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Project description:OBJECTIVES:To comprehensively ascertain the extent and severity of clinical features in affected individuals from 2 large families with proven heterozygous mutations in the CYLD locus and to correlate these findings with the 3 appendageal tumor predisposition syndromes (familial cylindromatosis, Brooke-Spiegler syndrome, and multiple familial trichoepitheliomas) known to be associated with such germline mutations. DESIGN:Interfamilial and intrafamilial observational study. SETTING:Tertiary genetic and dermatology referral center. PARTICIPANTS:Thirty-four individuals recruited from 2 large multigenerational families with CYLD mutations. Clinical details, history, and tumor maps were obtained from all participants; in 18, the information was corroborated by detailed clinical examination. MAIN OUTCOME MEASURES:Tumor density, distribution and histologic findings, associated medical conditions, patient symptoms, and impact of disease on quality of life. RESULTS:The severity of penetrance and phenotype varied within families. Although an approximately equal female to male predisposition was noted, 5 women and 1 man (of 26 patients surveyed [23%]) had undergone total scalp removal. The average age at onset was 16 years (range, 8-30 years). Symptoms reported by affected patients included painful tumors (in 12 of 23 patients [52%] who answered the question), conductive deafness, and sexual dysfunction. Of the 26 surveyed patients, tumors were noted on the scalp in 21 (81%), on the trunk in 18 (69%), and in the pubic area in 11 (42%). Tumor mapping provided clinical evidence that correlated with hormonally stimulated hair follicles being particularly vulnerable to loss of heterozygosity and tumor induction. CONCLUSIONS:The burden of disease at sites other than the head and neck appears to be underreported in the literature and greatly affects quality of life. Differentiation between the clinical diagnoses has little prognostic or clinical utility in genetic counseling, even within individuals from the same family. Thus, we suggest an encompassing diagnosis of "CYLD cutaneous syndrome." Finally, the clinical distribution of tumors suggests that hormonal factors may play an important role in tumor induction in these patients.

Project description:BackgroundPyroptosis and prostate cancer (PCa) are closely related. The role of pyroptosis-related long non-coding RNAs (lncRNAs) (PRLs) in PCa remains elusive. This study aimed to explore the relationship between PRL and PCa prognosis.MethodsGene expression and clinical signatures were obtained from The Cancer Genome Atlas and Gene Expression Omnibus databases. A PRL risk prediction model was established by survival random forest analysis and least absolute shrinkage and selection operator regression. Functional enrichment, immune status, immune checkpoints, genetic mutations, and drug susceptibility analyses related to risk scores were performed by the single-sample gene set enrichment analysis, gene set variation analysis, and copy number variation analysis. PRL expression was verified in PCa cells. Cell Counting Kit-8, 5-ethynyl-2'-deoxyuridine, wound healing, transwell, and Western blotting assay were used to detect the proliferation, migration, invasion, and pyroptosis of PCa cells, respectively.ResultsPrognostic features based on six PRL (AC129507.1, AC005253.1, AC127502.2, AC068580.3, LIMD1-AS1, and LINC01852) were constructed, and patients in the high-score group had a worse prognosis than those in the low-score group. This feature was determined to be independent by Cox regression analysis, and the area under the curve of the 1-, 3-, and 5-year receiver operating characteristic curves in the testing cohort was 1, 0.93, and 0.92, respectively. Moreover, the external cohort validation confirmed the robustness of the PRL risk prediction model. There was a clear distinction between the immune status of the two groups. The expression of multiple immune checkpoints was also reduced in the high-score group. Gene mutation proportion in the high-score group increased, and the sensitivity to drugs increased significantly. Six PRLs were upregulated in PCa cells. Silencing of AC005253.1 inhibited cell proliferation, migration, and invasion in DU145 and PC-3 cells. Moreover, silencing of AC005253.1 promoted pyroptosis and inflammasome AIM2 expression.ConclusionsOverall, we constructed a prognostic model of PCa with six PRLs and identified their expression in PCa cells. The experimental verification showed that AC005253.1 could affect the proliferation, migration, and invasion abilities of PCa cells. Meanwhile, AC005253.1 may play an important role in PCa by affecting pyroptosis through the AIM2 inflammasome. This result requires further research for verification.

Dataset Information

Induction of Pyroptosis and Its Implications in Cancer Management.

Publications

Induction of Pyroptosis and Its Implications in Cancer Management.

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