文章：

Tob通过与肿瘤坏死因子受体复合物的结合，在乳腺癌中负向调控NF-κB的激活

Tob negatively regulates NF-κB activation in breast cancer through its association with the TNF receptor complex 

原文发布日期：2025-04-01 

英文摘要：

NF-κB mediates transcriptional regulation crucial to many biological functions, and elevated NF-κB activity leads to autoimmune and inflammatory diseases, as well as cancer. Since highly aggressive breast cancers have few therapeutic molecular targets, clarification of key molecular mechanisms of NF-κB signaling would facilitate the development of more effective therapy. In this report, we show that Tob, a member of the Tob/BTG family of antiproliferative proteins, acts as a negative regulator of the NF-κB signal in breast cancer. Studies with 35 human breast cancer cell lines reveal that Tob expression is negatively correlated with NF-κB activity. Analysis of The Cancer Genome Atlas (TCGA) database of clinical samples reveals an inverse correlation between Tob expression and NF-κB activity. Tob knockdown in human breast cancer cells promoted overactivation of NF-κB upon TNF-α treatment, whereas overexpression of Tob inhibited TNF-α stimulation-dependent NF-κB activation. Mechanistically, Tob associates with the TNF receptor complex I and consequently inhibits RIPK1 polyubiquitylation, leading to possible prevention of overwhelming activation of NF-κB. 

摘要翻译：

NF-κB介导的转录调控对多种生物学功能至关重要，其活性升高会导致自身免疫性疾病、炎症性疾病以及癌症。由于高侵袭性乳腺癌的治疗分子靶点极少，阐明NF-κB信号传导的关键分子机制将有助于开发更有效的治疗方法。本研究表明，抗增殖蛋白Tob/BTG家族成员Tob在乳腺癌中作为NF-κB信号的负调控因子。通过对35种人类乳腺癌细胞系的研究发现，Tob表达与NF-κB活性呈负相关。对癌症基因组图谱（TCGA）临床样本数据库的分析显示，Tob表达与NF-κB活性存在负相关性。在人类乳腺癌细胞中敲低Tob会促进TNF-α处理后NF-κB的过度激活，而过表达Tob则抑制TNF-α刺激依赖的NF-κB活化。从机制上讲，Tob与TNF受体复合物I结合，从而抑制RIPK1的多聚泛素化，这可能有效防止NF-κB的过度激活。

原文链接：

Tob negatively regulates NF-κB activation in breast cancer through its association with the TNF receptor complex