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揭示 gasdermin B 在癌症和炎症性疾病中的作用:从分子机制到治疗策略

英文原题:Unveiling the role of gasdermin B in cancer and inflammatory disease: from molecular mechanisms to therapeutic strategies.

PubMed 2025/05/28(内容时间) PeerJ Q2 · IF 2.9(JCR 2025)

研究概要

作为一种多功能蛋白,GSDMB不仅参与细胞焦亡,还调控非焦亡过程,在癌症进展和炎症性疾病中发挥重要作用。

中文摘要

Gasdermin B(GSDMB)是gasdermin(GSDM)蛋白家族的成员,主要因介导细胞焦亡——一种炎症性程序性细胞死亡形式——而为人所知。近年来的研究揭示了GSDMB多样的分子功能及其与多种疾病的密切关联,尤其是癌症(如乳腺癌、胃癌、膀胱癌)和炎症性疾病(如哮喘、炎症性肠病)。在分子层面,GSDMB通过在细胞膜上形成孔洞诱导细胞焦亡,导致膜破裂。这一功能在GSDM蛋白家族中普遍存在;然而,GSDMB还表现出独特的非焦亡功能,如调节细胞增殖、迁移和免疫应答。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,通过与其信号通路如STAT3和丝裂原活化蛋白激酶(MAPK)/细胞外信号调节激酶(ERK)的相互作用,促进癌细胞增殖、侵袭和转移。此外,GSDMB通过其焦亡活性影响免疫微环境,在炎症的启动和调控中发挥作用。激活后,它可通过其N端结构域直接裂解靶细胞,对慢性炎症性疾病和NK细胞介导的抗菌反应有重要贡献。总之,作为一种多功能蛋白,GSDMB不仅参与细胞焦亡,还调控非焦亡过程,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。

展开英文摘要原文

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 ( e.g. , breast cancer, gastric cancer, bladder cancer) and inflammatory diseases ( e.g. , 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 via 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.

论文信息

作者
Yang W、Hu X、Li X
单位
West China Medical School, Sichuan University, Department of Urology, Institute of Urology, Chengdu, Sichuan, China.China
文献类型
综述
期刊
PeerJ2025
原文标识
PubMed 40452932 · DOI 10.7717/peerj.19392