Wang Man, Chen Xinzhe, Zhang Yuan
Institute for Translational Medicine, The Affiliated Hospital of Qingdao University, Qingdao, China.
Front Cell Dev Biol. 2021 Feb 9;9:638710. doi: 10.3389/fcell.2021.638710. eCollection 2021.
Pyroptosis is a type of lytic programmed cell death triggered by various inflammasomes that sense danger signals. Pyroptosis has recently attracted great attention owing to its contributory role in cancer. Pyroptosis plays an important role in cancer progression by inducing cancer cell death or eliciting anticancer immunity. The participation of gasdermins (GSDMs) in pyroptosis is a noteworthy recent discovery. GSDMs have emerged as a group of pore-forming proteins that serve important roles in innate immunity and are composed of GSDMA-E and Pejvakin (PJVK) in human. The N-terminal domains of GSDMs, expect PJVK, can form pores on the cell membrane and function as effector proteins of pyroptosis. Remarkably, it has been found that GSDMs are abnormally expressed in several forms of cancers. Moreover, GSDMs are involved in cancer cell growth, invasion, metastasis and chemoresistance. Additionally, increasing evidence has indicated an association between GSDMs and clinicopathological features in cancer patients. These findings suggest the feasibility of using GSDMs as prospective biomarkers for cancer diagnosis, therapeutic intervention and prognosis. Here, we review the progress in unveiling the characteristics and biological functions of GSDMs. We also focus on the implication and molecular mechanisms of GSDMs in cancer pathogenesis. Investigating the relationship between GSDMs and cancer biology could assist us to explore new therapeutic avenues for cancer prevention and treatment.
细胞焦亡是一种由多种可感知危险信号的炎性小体触发的溶解性程序性细胞死亡。由于其在癌症中的作用，细胞焦亡最近备受关注。细胞焦亡通过诱导癌细胞死亡或引发抗癌免疫在癌症进展中发挥重要作用。gasdermin（GSDM）参与细胞焦亡是最近一项值得注意的发现。GSDM已成为一组在先天免疫中起重要作用的成孔蛋白，在人类中由GSDMA - E和佩吉瓦金（PJVK）组成。除PJVK外，GSDM的N端结构域可在细胞膜上形成孔，并作为细胞焦亡的效应蛋白发挥作用。值得注意的是，已发现GSDM在多种癌症中异常表达。此外，GSDM参与癌细胞的生长、侵袭、转移和化疗耐药性。此外，越来越多的证据表明GSDM与癌症患者的临床病理特征之间存在关联。这些发现表明将GSDM用作癌症诊断、治疗干预和预后的潜在生物标志物具有可行性。在此，我们综述了揭示GSDM特征和生物学功能的研究进展。我们还关注GSDM在癌症发病机制中的意义和分子机制。研究GSDM与癌症生物学之间的关系有助于我们探索癌症预防和治疗的新途径。
