GSDMD在恶性肿瘤中的研究进展

Research Progress of GSDMD in Malignant Tumor

GSDMD是细胞焦亡的重要执行蛋白之一,被胱天蛋白酶(caspase)-1或胞内脂多糖的受体caspase-4/-5/-11所识别和切割,释放出GSDMD N端的膜打孔活性,破坏细胞膜内外离子梯度和水平衡,导致细胞胀大直至裂解,从而释放白细胞介素(IL)-1β、IL-18、高迁移率族蛋白B1等促炎性细胞因子和细胞内容物,最终引发细胞焦亡。GSDMD介导的细胞焦亡在恶性肿瘤的发生发展中扮演促进和抑制肿瘤的双重角色,并与肿瘤的侵袭和预后密切相关。此外,GSDMD还可通过焦亡非依赖的方式提高化疗药物对肿瘤的杀伤作用。因此,了解GSDMD的结构、功能及其在恶性肿瘤中的分子作用可为抗肿瘤诊疗提供新思路。

Gasdermin D(GSDMD)is one of the important executive proteins of pyroptosis.It is recognized and cleaved by caspase-1 or intracellular lipopolysaccharide receptor caspase-4,5,and 11,releasing the membrane perforation activity at the N-terminus of GSDMD,destroying the ion gradient and water balance inside and outside the cell membrane,leading to cell swelling and cracking,releasing pro-inflammatory cytokines and cell contents such as interleukin(IL)-1,IL-18,and high mobility group protein B1,thereby triggering pyroptosis.GSDMD-mediated pyroptosis plays a dual role in promoting and inhibiting tumor development and is closely related to tumor invasion and prognosis.Furthermore,GSDMD can also enhance the killing effect of chemotherapeutic drugs on tumors in a pyroptosis-independent manner.Therefore,understanding the structure and function of GSDMD and its molecular role in malignant tumors can provide new ideas for anti-tumor diagnosis and treatment.