Gasdermin家族调控肿瘤细胞焦亡的研究进展

Research Progress on Gasdermin Family in Pyroptosis of Cancer

细胞焦亡是一种炎症性程序性死亡方式,是一种有别于传统的坏死、凋亡等的新型细胞死亡方式。Gasdermin(GSDM)蛋白家族在细胞焦亡过程中发挥重要作用,由Gasdermin A(GSDMA)、Gasdermin B(GSDMB)、Gasdermin C(GSDMC)、Gasdermin D(GSDMD)、Gasdermin E(GSDME)和DFNB59组成。活化的半胱氨酸天冬氨酸特异性蛋白酶(caspase)切割Gasdermin家族成员释放N端结构域在胞膜上打孔,从而导致细胞肿胀破裂死亡的过程。近年,细胞焦亡在肿瘤中的作用受到学者广泛关注。研究表明,焦亡可能在肿瘤的发生及治疗机制中起双刃剑作用。一方面,正常细胞受到刺激发生焦亡的过程中释放大量炎性因子,形成炎性微环境导致正常细胞转化为肿瘤细胞。另一方面,诱导肿瘤细胞发生焦亡可以作为一个新的治疗靶点抑制肿瘤的发生和发展。本文将对GSDM家族调控肿瘤细胞焦亡的作用作一综述,以期提出细胞焦亡这一新的临床肿瘤防治方向。

Pyroptosis is a form of lytic programmed cell death,which is different from the traditional programmed cell death such as necrosis and apoptosis.The Gasdermin(GASDM)family includes Gasdermin A(GSDMA),Gasdermin B(GSDMB),Gasdermin C(GSDMC),Gasdermin D(GSDMD),Gasdermin E(GSDME)and DFNB59;and it plays an important role in pyroptosis.The activated cysteinyl aspartate specific proteinase(caspase)cleaves GSDM and separates its GSDM-N domain to form pores in the cell membrane that drive swelling and membrane rupture.In recent years,pyroptosis in cancer has attracted extensive attention.Studies have shown that pyroptosis might be a double-edged sword in the pathogenesis and treatment of cancer.On the one hand,large number of inflammatory factors are released during the process of pyroptosis when normal cells are stimulated,forming an inflammatory microenvironment that leads to the transformation of normal cells into cancer cells.On the other hand,pyroptosis in cancer cells can be used as a new therapeutic target to inhibit the occurrence and development of cancer.This review focuses on the role of GSDM family in pyroptosis of cancer to provide a new ideas for clinic prevention and treatment for cancer.