Yang Weixiao, Hu Xu, Li Xiang
West China Medical School, Sichuan University, Department of Urology, Institute of Urology, Chengdu, Sichuan, China.
PeerJ. 2025 May 28;13:e19392. doi: 10.7717/peerj.19392. eCollection 2025.
Gasdermin B (GSDMB) is a member of the gasdermin (GSDM) protein family, primarily known for mediating pyroptosis, an inflammatory form of programmed cell death. Recent studies have revealed the diverse molecular functions of GSDMB and its close association with various diseases, particularly cancers (, breast cancer, gastric cancer, bladder cancer) and inflammatory diseases (, asthma, inflammatory bowel disease). At the molecular level, GSDMB induces pyroptosis by forming pores in the cell membrane, leading to membrane rupture. This function is common across the GSDM protein family; however, GSDMB also exhibits unique non-pyroptotic functions, such as modulating cell proliferation, migration, and immune responses. In multiple cancers, including breast cancer, gastric cancer, and cervical cancer, high expression of GSDMB correlates with poor prognosis, promoting cancer cell proliferation, invasion, and metastasis through interactions with signaling pathways such as STAT3 and mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK). Additionally, GSDMB influences the immune microenvironment through its pyroptotic activity, playing a role in the initiation and regulation of inflammation. Upon activation, it can directly cleave target cells its N-terminal domain, contributing significantly to chronic inflammatory diseases and NK cell-mediated antibacterial responses. In conclusion, as a multifunctional protein, GSDMB not only participates in pyroptosis but also regulates non-pyroptotic processes, playing an important role in cancer progression and inflammatory diseases. Further elucidating the detailed mechanisms of GSDMB may offer novel therapeutic avenues for these conditions.
Gasdermin B（GSDMB）是gasdermin（GSDM）蛋白家族的成员，主要以介导细胞焦亡而闻名，细胞焦亡是一种程序性细胞死亡的炎症形式。最近的研究揭示了GSDMB的多种分子功能及其与各种疾病，特别是癌症（如乳腺癌、胃癌、膀胱癌）和炎症性疾病（如哮喘、炎症性肠病）的密切关联。在分子水平上，GSDMB通过在细胞膜上形成孔道诱导细胞焦亡，导致膜破裂。这种功能在GSDM蛋白家族中是常见的；然而，GSDMB还表现出独特的非细胞焦亡功能，如调节细胞增殖、迁移和免疫反应。在包括乳腺癌、胃癌和宫颈癌在内的多种癌症中，GSDMB的高表达与不良预后相关，通过与信号通路如信号转导和转录激活因子3（STAT3）以及丝裂原活化蛋白激酶（MAPK）/细胞外信号调节激酶（ERK）相互作用促进癌细胞增殖、侵袭和转移。此外，GSDMB通过其细胞焦亡活性影响免疫微环境，在炎症的起始和调节中发挥作用。激活后，它可以通过其N端结构域直接裂解靶细胞，对慢性炎症性疾病和自然杀伤细胞介导的抗菌反应有显著贡献。总之，作为一种多功能蛋白，GSDMB不仅参与细胞焦亡，还调节非细胞焦亡过程，在癌症进展和炎症性疾病中发挥重要作用。进一步阐明GSDMB的详细机制可能为这些疾病提供新的治疗途径。
