TNF-α和TNFR与多信号衔接蛋白协同调控在乳腺癌中发挥的多效性生物学作用  

The pleipotent biological effects of tumor necrosis factor alpha,tumor necrosis factor receptor and multi-signal adaptor proteins in synergistic regulation in breast cancer

作　　者：徐厉程 符湛培 吴冶琴 王刚平 Xu Licheng;Fu Zhanpei;Wu Yeqin;Wang Gangping(Department of Clinical Laboratory,the Fourth Affiliated Hospital,Zhejiang University School of Medicine,International School of Medicine,Zhejiang University,International Institute of Health Medicine,Zhejiang University,Yiwu,Zhejiang 322000,China;Department of Pathology,the Fourth Affiliated Hospital,Zhejiang University School of Medicine,International School of Medicine,Zhejiang University,International Institute of Health Medicine,Zhejiang University,Yiwu,Zhejiang 322000,China;Central Laboratory of Rizhao People's Hospital,Rizhao,Shandong 322000,China)

机构地区：[1]浙江大学医学院附属第四医院,浙江大学国际医学院,浙江大学国际健康医学研究院,检验医学中心,浙江义乌322000 [2]浙江大学医学院附属第四医院,浙江大学国际医学院,浙江大学国际健康医学研究院,病理科,浙江义乌322000 [3]日照市人民医院中心实验室,山东日照276826

出　　处：《感染、炎症、修复》2025年第2期127-133,共7页Infection Inflammation Repair

基　　金：山东省自然科学基金资助项目(ZR2020MH319)。

摘　　要：乳腺癌发病率居女性恶性肿瘤首位,是全球公共卫生问题。本文综述了肿瘤坏死因子-α(TNF-α)及TNF-α受体(TNFR)1和TNFR2在乳腺癌中的选择性靶向作用及相关治疗策略,TNFR1和TNFR2在不同的乳腺癌亚型中的表达及功能,TNF-α诱导的细胞凋亡和抗凋亡双重生物学效应及作用机制。TNF-α和TNFR通过与多种信号衔接蛋白作用,抑制信号转导和转录激活因子5(STAT5)磷酸化,影响乳腺细胞功能,通过肿瘤微环境中免疫细胞功能影响免疫逃逸和耐药性,抵抗TNF-α诱导的凋亡,诱导乳腺癌的肿瘤干性和上皮-间质转化。复杂的信号转导机制及与不同受体结合后发挥作用不尽相同的特性使得TNF-α在细胞信号转导中具有高度的特异性和复杂性,提示选择性靶向TNFR1和TNFR2可能比传统的全TNF阻断疗法更具优势。Breast cancer ranks first in the incidence rate of malignant tumors among women,posing a global public health issue.This article reviews the selective targeting effects of tumor necrosis factor alpha(TNF-α)and tumor necrosis factor receptor(TNFR)1 and TNFR2 in breast cancer and related therapeutic strategies,the expression and functions of TNFR1 and TNFR2 in different subtypes of breast cancer,as well as the dual biological effects and mechanisms of TNF-αinduced apoptosis and anti-apoptosis.TNF-αand TNFR inhibit the phosphorylation of signal transducer and activator of transcription 5(STAT5)by interacting with multiple signal adaptor proteins,affect the function of breast cells,influence immune escape and drug resistance through the function of immune cells in the tumor microenvironment,resist TNF-αinduced apoptosis,and induce tumor stemness and epithelial-mesenchymal transition of breast cancer.The complex signal transduction mechanism and the characteristic of playing different roles after binding to different receptors make TNF-αhighly specific and complex in cellular signal transduction,suggesting that selective targeting of TNFR1 and TNFR2 may have more advantages than the traditional total TNF blocking therapy.

关 键 词：乳腺癌 肿瘤坏死因子-α 肿瘤坏死因子-α受体 核因子-κB 肿瘤微环境 肿瘤干性 上皮-间质转化 

分 类 号：R737.9[医药卫生—肿瘤]