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关联NF-κB激活的TNFR1和TNFR2,驱动肺癌的进展,细胞分化和转移

Gongping Shi¹, Yinling Hu¹

¹Cancer Innovation Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD 21702, USA.

|September 9, 2023

概括

瘤坏死因子受体 (TNFR1和TNFR2) 促进肺癌的进展. TNFR1驱动肺状细胞癌转移,而TNFR2有助于肺腺癌的生长,这表明潜在的治疗点.

科学领域:

在瘤学瘤学.
免疫学免疫学免疫学
分子生物学分子生物学

背景情况:

肺癌是癌症死亡的主要原因之一.
瘤坏死因子受体 (TNFR1和TNFR2) 在肺癌中的作用尚未完全理解.
TNFR1和TNFR2是TNFR超级家族的关键成员,具有不同的表达模式.

研究的目的:

审查最近关于TNFR1和TNFR2在肺状细胞癌 (SCC) 和肺腺癌 (ADC) 发展中的作用的发现.
基于TNFR信号传递,突出人类肺癌的潜在治疗点.
阐明TNFRs对肺瘤发生有助的机制.

主要方法:

对人类肺部SCC和ADC患者队列的分析.
在一个结合自发性肺SCC和TNFR1转基因小鼠模型中的研究.
检查分子通路,包括NF-κB,c-Rel和基因表达特征.

主要成果:

肺SCC中过度表达的TNFR1与增加的UBCH10相关,促进脱差,上皮-介质细胞过渡和转移.
UBCH10的TNFR1上调包括c-Rel和p65NF-κB的激活.
TNFR2对于通过TNF/TNFR2/NF-κB-c-Rel途径的肺ADC进展至关重要,其中涉及巨细胞衍生的ROS和TNF诱导的Treg细胞生成.
肺ADC中的TNFRSF1B表达与TNF,FOXP3和CD4表达相关.

结论:

通过不同的机制,TNFR1和TNFR2在肺SCC和ADC发育中发挥着重要作用.
准TNFR1和TNFR2通路为人类肺癌提供了一个有前途的治疗策略.
了解瘤微环境中的TNFR信号对于开发有效的肺癌治疗非常重要.

关键词:

在 NF-κBB 中.这就是TNFR1的特点.这就是TNFR2的特点.肺部腺癌的癌症.肺状细胞癌是肺的状细胞癌.

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