Wang Yueyuan, Peng Jingyu, Xie Xiao, Zhang Zhihao, Li Mingxi, Yang Ming
Department of Breast Surgery, The First Hospital of Jilin University, Changchun, People's Republic of China.
Department of Neurology and Neuroscience Center, The First Hospital of Jilin University, Changchun, People's Republic of China.
J Cancer. 2021 Jun 26;12(17):5241-5248. doi: 10.7150/jca.48989. eCollection 2021.
Hearing loss-associated protein gasdermin E (GSDME), an effector of secondary necrosis, has been identified in a new pathway of programmed cell death (PCD). GSDME epigenetic silencing and mutations resulting in loss-of-function have been reported in cancer tissues. Additionally, GSDME upregulation inhibits tumor proliferation as well as colony forming ability, and reduces the incidence of lymphatic metastasis, demonstrating that GSDME may act as a tumor suppressor. Here, we have focused on the molecular mechanisms of GSDME-mediated PCD, and tried to reveal the crosstalk between this cell death pathway and apoptosis, autophagy, GSDMD-mediated pyroptosis. Moreover, we concluded the anti-cancer activity of GSDME include forming permeable membranes, and triggering anti-cancer immunity. Thus, GSDME was potential to be a novel target for cancer prevention and treatment.
与听力损失相关的蛋白Gasdermin E（GSDME）是继发性坏死的效应器，已在一种新的程序性细胞死亡（PCD）途径中被鉴定出来。在癌症组织中已报道了GSDME的表观遗传沉默和导致功能丧失的突变。此外，GSDME的上调抑制肿瘤增殖以及集落形成能力，并降低淋巴转移的发生率，表明GSDME可能作为一种肿瘤抑制因子发挥作用。在此，我们聚焦于GSDME介导的PCD的分子机制，并试图揭示这种细胞死亡途径与凋亡、自噬、GSDMD介导的焦亡之间的相互作用。此外，我们得出结论，GSDME的抗癌活性包括形成可渗透膜和触发抗癌免疫。因此，GSDME有潜力成为癌症预防和治疗的新靶点。
