First Department of Pediatrics, National and Kapodistrian University of Athens, Thivon & Levadeias 8, 11527, Goudi-Athens, Greece.
Mol Biol Rep. 2020 May;47(5):4047-4063. doi: 10.1007/s11033-020-05410-w. Epub 2020 Apr 1.
Disruption of tissue function activates cellular stress which triggers a number of mechanisms that protect the tissue from further damage. These mechanisms involve a number of homeostatic modules, which are regulated at the level of gene expression by the transactivator NF-κB. This transcription factor shifts between activation and repression of discrete, cell-dependent gene expression clusters. Some of its target genes provide feedback to NF-κB itself, thereby strengthening the inflammatory response of the tissue and later terminating inflammation to facilitate restoration of tissue homeostasis. Disruption of key feedback modules for NF-κB in certain cell types facilitates the survival of clones with genomic aberrations, and protects them from being recognized and eliminated by the immune system, to enable thereby carcinogenesis.
组织功能的紊乱会激活细胞应激，从而触发许多保护组织免受进一步损伤的机制。这些机制涉及许多体内平衡模块，它们在基因表达水平上受到转录因子 NF-κB 的调节。这种转录因子在离散的、细胞依赖性基因表达簇的激活和抑制之间转换。其一些靶基因本身为 NF-κB 提供反馈，从而增强组织的炎症反应，随后终止炎症以促进组织内稳态的恢复。在某些细胞类型中，NF-κB 的关键反馈模块的破坏促进了具有基因组异常的克隆的存活，并保护它们免受免疫系统的识别和消除，从而促进了癌变。
