GSDME在恶性肿瘤中的研究现状

doi:10.3760/cma.j.cn371439-20230123-00057

摘要/Abstract

摘要：

细胞焦亡是一种区别于凋亡和坏死的细胞程序性死亡，其发生过程伴随着细胞膜的裂解和细胞内容物的释放。细胞焦亡由Gasdermin蛋白家族介导发生，并且依赖于caspase的活性。GSDME是Gasdermin蛋白超家族的重要成员之一，在其介导的细胞焦亡中依赖于caspase-3的活性。近年来，随着对细胞焦亡的进一步研究，GSDME诱导细胞焦亡的机制逐渐明确。众多研究表明GSDME介导的细胞焦亡在肿瘤的发生发展及化疗耐药中起重要作用。然而GSDME介导的细胞焦亡没有特异性，在诱导肿瘤细胞焦亡的同时，可诱导机体的正常细胞发生焦亡，从而对机体的各个器官造成不同程度的损伤。深入研究GSDME诱导细胞焦亡的机制、GSDME在恶性肿瘤中的作用及其化疗不良反应，可为肿瘤的监测、治疗及判断预后提供新的思路。

关键词: 肿瘤, GSDME, 细胞焦亡

Abstract:

Pyroptosis is a type of programmed cell death distincted from apoptosis and necrosis， which is accompanied by the lysis of cell membranes and the release of cell contents. Pyroptosis occurs as mediated by Gasdermin protein family and is dependent on the activity of caspase. GSDME is one of the most important members of the Gasdermin protein superfamily. GSDME-mediated pyroptosis relies on the activity of caspase-3. In recent years， with further research on pyroptosis， the mechanism of GSDME-induced pyroptosis is becoming clear. Numerous studies have shown that GSDME-mediated pyroptosis plays an important role in the occurrence and development of tumors， as well as chemotherapy resistance. However， GSDME-mediated pyroptosis has no specificity and can induce pyroptosis of normal cells in the body while inducing tumor cell pyroptosis， thus causing different degrees of damage to various organs of the body. Further study on the mechanism of GSDME-induced pyroptosis， the role of GSDME in malignant tumors and the adverse reactions of chemotherapy can provide new ideas for tumor monitoring， treatment and prognosis judgment.

Key words: Neoplasms, GSDME, Pyroptosis

张渊, 冯勤梅, 马梅杰, 白芷玉, 李琪. GSDME在恶性肿瘤中的研究现状[J]. 国际肿瘤学杂志, 2023, 50(5): 285-289.

Zhang Yuan, Feng Qinmei, Ma Meijie, Bai Zhiyu, Li Qi. Current status of GSDME research in malignant tumors[J]. Journal of International Oncology, 2023, 50(5): 285-289.

参考文献 39

[1]	De Schutter E, Croes L, Ibrahim J, et al. GSDME and its role in cancer: from behind the scenes to the front of the stage[J]. Int J Cancer, 2021, 148(12): 2872-2883. DOI: 10.1002/ijc.33390. doi: 10.1002/ijc.33390 pmid: 33186472
[2]	Saeki N, Kuwahara Y, Sasaki H, et al. Gasdermin (Gsdm) locali-zing to mouse chromosome 11 is predominantly expressed in upper gastrointestinal tract but significantly suppressed in human gastric cancer cells[J]. Mamm Genome, 2000, 11(9): 718-724. DOI: 10. 1007/s003350010138. doi: 10.1007/s003350010138 pmid: 10967128
[3]	Ibrahim J, Op de Beeck K, Fransen E, et al. Methylation analysis of Gasdermin E shows great promise as a biomarker for colorectal cancer[J]. Cancer Med, 2019, 8(5): 2133-2145. DOI: 10.1002/cam4.2103. doi: 10.1002/cam4.2103
[4]	Wang Y, Gao W, Shi X, et al. Chemotherapy drugs induce pyroptosis through caspase-3 cleavage of a gasdermin[J]. Nature, 2017, 547(7661): 99-103. DOI: 10.1038/nature22393. doi: 10.1038/nature22393
[5]	张依格, 高军, 王建榜. GSDME介导的细胞焦亡在肿瘤发生发展中的作用及其临床意义[J]. 中国肿瘤生物治疗杂志, 2021, 28(3): 288-293. DOI: 10.3872/j.issn.1007-385x.2021.03.011. doi: 10.3872/j.issn.1007-385x.2021.03.011
[6]	Jiang M, Qi L, Li L, et al. The caspase-3/GSDME signal pathway as a switch between apoptosis and pyroptosis in cancer[J]. Cell Death Discov, 2020, 6: 112. DOI: 10.1038/s41420-020-00349-0. doi: 10.1038/s41420-020-00349-0 pmid: 33133646
[7]	Hu L, Chen M, Chen X, et al. Chemotherapy-induced pyroptosis is mediated by BAK/BAX-caspase-3-GSDME pathway and inhibited by 2-bromopalmitate[J]. Cell Death Dis, 2020, 11(4): 281. DOI: 10.1038/s41419-020-2476-2. doi: 10.1038/s41419-020-2476-2 pmid: 32332857
[8]	Yang F, Bettadapura SN, Smeltzer MS, et al. Pyroptosis and pyroptosis-inducing cancer drugs[J]. Acta Pharmacol Sin, 2022, 43(10): 2462-2473. DOI: 10.1038/s41401-022-00887-6. doi: 10.1038/s41401-022-00887-6 pmid: 35288674
[9]	Zhang Z, Zhang Y, Xia S, et al. Gasdermin E suppresses tumour growth by activating anti-tumour immunity[J]. Nature, 2020, 579(7799): 415-420. DOI: 10.1038/s41586-020-2071-9. doi: 10.1038/s41586-020-2071-9
[10]	Wu F, Wang L, Zhou C. Lung cancer in China: current and prospect[J]. Curr Opin Oncol, 2021, 33(1): 40-46. DOI: 10.1097/CCO.0000000000000703. doi: 10.1097/CCO.0000000000000703 pmid: 33165004
[11]	高世华, 李植锋, 蔡键锋. GSDME通过p53、caspase3增强小细胞肺癌细胞的紫杉醇敏感[J]. 医学研究杂志, 2021, 50(10): 138-142. DOI: 10.11969/j.issn.1673-548X.2021.10.030. doi: 10.11969/j.issn.1673-548X.2021.10.030
[12]	Zhang CC, Li CG, Wang YF, et al. Chemotherapeutic paclitaxel and cisplatin differentially induce pyroptosis in A549 lung cancer cells via caspase-3/GSDME activation[J]. Apoptosis, 2019, 24(3/4): 312-325. DOI: 10.1007/s10495-019-01515-1. doi: 10.1007/s10495-019-01515-1
[13]	Peng Z, Wang P, Song W, et al. GSDME enhances cisplatin sensitivity to regress non-small cell lung carcinoma by mediating pyroptosis to trigger antitumor immunocyte infiltration[J]. Signal Transduct Target Ther, 2020, 5(1): 159. DOI: 10.1038/s41392-020-00274-9. doi: 10.1038/s41392-020-00274-9
[14]	Lu H, Zhang S, Wu J, et al. Molecular targeted therapies elicit concurrent apoptotic and GSDME-dependent pyroptotic tumor cell death[J]. Clin Cancer Res, 2018, 24(23): 6066-6077. DOI: 10.1158/1078-0432.CCR-18-1478. doi: 10.1158/1078-0432.CCR-18-1478 pmid: 30061362
[15]	Li W, Xu R, Zhu B, et al. Circular RNAs: functions and mechanisms in nasopharyngeal carcinoma[J]. Head Neck, 2022, 44(2): 494-504. DOI: 10.1002/hed.26962. doi: 10.1002/hed.26962
[16]	Guan S, Wei J, Huang L, et al. Chemotherapy and chemo-resistance in nasopharyngeal carcinoma[J]. Eur J Med Chem, 2020, 207: 112758. DOI: 10.1016/j.ejmech.2020.112758. doi: 10.1016/j.ejmech.2020.112758
[17]	Cai J, Yi M, Tan Y, et al. Natural product triptolide induces GSDME-mediated pyroptosis in head and neck cancer through suppressing mitochondrial hexokinase-Ⅱ[J]. J Exp Clin Cancer Res, 2021, 40(1): 190. DOI: 10.1186/s13046-021-01995-7. doi: 10.1186/s13046-021-01995-7
[18]	Li Q, Wang M, Zhang Y, et al. BIX-01294-enhanced chemosensitivity in nasopharyngeal carcinoma depends on autophagy-induced pyroptosis[J]. Acta Biochim Biophys Sin (Shanghai), 2020, 52(10): 1131-1139. DOI: 10.1093/abbs/gmaa097. doi: 10.1093/abbs/gmaa097
[19]	Di M, Miao J, Pan Q, et al. OTUD4-mediated GSDME deubiquitination enhances radiosensitivity in nasopharyngeal carcinoma by inducing pyroptosis[J]. J Exp Clin Cancer Res, 2022, 41(1): 328. DOI: 10.1186/s13046-022-02533-9. doi: 10.1186/s13046-022-02533-9
[20]	Yin J, Che G, Wang W, et al. Investigating the prognostic significance of pyroptosis-related genes in gastric cancer and their impact on cells' biological functions[J]. Front Oncol, 2022, 12: 861284. DOI: 10.3389/fonc.2022.861284. doi: 10.3389/fonc.2022.861284
[21]	Kim MS, Chang X, Yamashita K, et al. Aberrant promoter me-thylation and tumor suppressive activity of the DFNA5 gene in colorectal carcinoma[J]. Oncogene, 2008, 27(25): 3624-3634. DOI: 10.1038/sj.onc.1211021. doi: 10.1038/sj.onc.1211021 pmid: 18223688
[22]	Wu M, Wang Y, Yang D, et al. A PLK1 kinase inhibitor enhances the chemosensitivity of cisplatin by inducing pyroptosis in oesophageal squamous cell carcinoma[J]. EBioMedicine, 2019, 41: 244-255. DOI: 10.1016/j.ebiom.2019.02.012. doi: S2352-3964(19)30084-2 pmid: 30876762
[23]	Yu J, Li S, Qi J, et al. Cleavage of GSDME by caspase-3 determines lobaplatin-induced pyroptosis in colon cancer cells[J]. Cell Death Dis, 2019, 10(3): 193. DOI: 10.1038/s41419-019-1441-4. doi: 10.1038/s41419-019-1441-4 pmid: 30804337
[24]	Zhang X, Zhang P, An L, et al. Miltirone induces cell death in hepatocellular carcinoma cell through GSDME-dependent pyroptosis[J]. Acta Pharm Sin B, 2020, 10(8): 1397-1413. DOI: 10.1016/j.apsb.2020.06.015. doi: 10.1016/j.apsb.2020.06.015 pmid: 32963939
[25]	Kashyap D, Pal D, Sharma R, et al. Global increase in breast cancer incidence: risk factors and preventive measures[J]. Biomed Res Int, 2022, 2022: 9605439. DOI: 10.1155/2022/9605439. doi: 10.1155/2022/9605439
[26]	Garcia-Martinez L, Zhang Y, Nakata Y, et al. Epigenetic mechanisms in breast cancer therapy and resistance[J]. Nat Commun, 2021, 12(1): 1786. DOI: 10.1038/s41467-021-22024-3. doi: 10.1038/s41467-021-22024-3 pmid: 33741974
[27]	Zhang Z, Zhang H, Li D, et al. Caspase-3-mediated GSDME induced pyroptosis in breast cancer cells through the ROS/JNK signalling pathway[J]. J Cell Mol Med, 2021, 25(17): 8159-8168. DOI: 10.1111/jcmm.16574. doi: 10.1111/jcmm.16574 pmid: 34369076
[28]	Croes L, Beyens M, Fransen E, et al. Large-scale analysis of DFNA5 methylation reveals its potential as biomarker for breast cancer[J]. Clin Epigenetics, 2018, 10: 51. DOI: 10.1186/s13148-018-0479-y. doi: 10.1186/s13148-018-0479-y
[29]	弓伟华. MCF7/Taxol细胞中DNA甲基化调控GSDME表达及在化疗耐药中的作用[D]. 郑州: 郑州大学, 2021. DOI: 10.27466/d.cnki.gzzdu.2021.002365. doi: 10.27466/d.cnki.gzzdu.2021.002365
[30]	Wang Y, Peng J, Mi X, et al. p53-GSDME elevation: a path for CDK7 inhibition to suppress breast cancer cell survival[J]. Front Mol Biosci, 2021, 8: 697457. DOI: 10.3389/fmolb.2021.697457. doi: 10.3389/fmolb.2021.697457
[31]	Zhou B, Zhang JY, Liu XS, et al. Tom20 senses iron-activated ROS signaling to promote melanoma cell pyroptosis[J]. Cell Res, 2018, 28(12): 1171-1185. DOI: 10.1038/s41422-018-0090-y. doi: 10.1038/s41422-018-0090-y pmid: 30287942
[32]	Zheng Z, Bian Y, Zhang Y, et al. Metformin activates AMPK/SIRT1/NF-κB pathway and induces mitochondrial dysfunction to drive caspase3/GSDME-mediated cancer cell pyroptosis[J]. Cell Cycle, 2020, 19(10): 1089-1104. DOI: 10.1080/15384101.2020.1743911. doi: 10.1080/15384101.2020.1743911 pmid: 32286137
[33]	Liu Y, Fang Y, Chen X, et al. Gasdermin E-mediated target cell pyroptosis by CAR T cells triggers cytokine release syndrome[J]. Sci Immunol, 2020, 5(43): eaax7969. DOI: 10.1126/sciimmunol.aax7969. doi: 10.1126/sciimmunol.aax7969
[34]	Berkel C, Cacan E. Differential expression and copy number variation of gasdermin (GSDM) family members, pore-forming proteins in pyroptosis, in normal and malignant serous ovarian tissue[J]. Inflammation, 2021, 44(6): 2203-2216. DOI: 10.1007/s10753-021-01493-0. doi: 10.1007/s10753-021-01493-0 pmid: 34091823
[35]	Kobayashi T, Mitsuhashi A, Hongying P, et al. Bexarotene-induced cell death in ovarian cancer cells through caspase-4-gasdermin E mediated pyroptosis[J]. Sci Rep, 2022, 12(1): 11123. DOI: 10.1038/s41598-022-15348-7. doi: 10.1038/s41598-022-15348-7 pmid: 35778597
[36]	李婷婷, 刘申平, 杜明. Gasdermin E多肽抑制剂对卵巢癌化疗诱导肠道损伤的改善作用[J]. 中国临床医学, 2022, 29(1): 35-41 DOI: 10.12025/j.issn.1008-6358.2022.20211121. doi: 10.12025/j.issn.1008-6358.2022.20211121
[37]	Tan G, Huang C, Chen J, et al. HMGB1 released from GSDME-mediated pyroptotic epithelial cells participates in the tumorigenesis of colitis-associated colorectal cancer through the ERK1/2 pathway[J]. J Hematol Oncol, 2020, 13(1): 149. DOI: 10.1186/s13045-020-00985-0. doi: 10.1186/s13045-020-00985-0
[38]	Shen X, Wang H, Weng C, et al. Caspase 3/GSDME-dependent pyroptosis contributes to chemotherapy drug-induced nephrotoxicity[J]. Cell Death Dis, 2021, 12(2): 186. DOI: 10.1038/s41419-021-03458-5. doi: 10.1038/s41419-021-03458-5 pmid: 33589596
[39]	Zhang Y, Chen X, Gueydan C, et al. Plasma membrane changes during programmed cell deaths[J]. Cell Res, 2018, 28(1): 9-21. DOI: 10.1038/cr.2017.133. doi: 10.1038/cr.2017.133 pmid: 29076500