Division of Hematology/Oncology, Department of Medicine, Rhode Island Hospital, Warren Alpert Medical School of Brown University, One Hoppin St., Coro West, Suite 5.01, RI, 02903, Providence, USA.
Cell Commun Signal. 2023 Oct 18;21(1):291. doi: 10.1186/s12964-023-01207-z.
NF-κB transcription factors are critical regulators of innate and adaptive immunity and major mediators of inflammatory signaling. The NF-κB signaling is dysregulated in a significant number of cancers and drives malignant transformation through maintenance of constitutive pro-survival signaling and downregulation of apoptosis. Overactive NF-κB signaling results in overexpression of pro-inflammatory cytokines, chemokines and/or growth factors leading to accumulation of proliferative signals together with activation of innate and select adaptive immune cells. This state of chronic inflammation is now thought to be linked to induction of malignant transformation, angiogenesis, metastasis, subversion of adaptive immunity, and therapy resistance. Moreover, accumulating evidence indicates the involvement of NF-κB signaling in induction and maintenance of invasive phenotypes linked to epithelial to mesenchymal transition (EMT) and metastasis. In this review we summarize reported links of NF-κB signaling to sequential steps of transition from epithelial to mesenchymal phenotypes. Understanding the involvement of NF-κB in EMT regulation may contribute to formulating optimized therapeutic strategies in cancer. Video Abstract.
NF-κB 转录因子是先天和适应性免疫的关键调节剂,也是炎症信号转导的主要介质。NF-κB 信号转导在大量癌症中失调,通过维持组成性生存信号和下调细胞凋亡来驱动恶性转化。过度活跃的 NF-κB 信号导致促炎细胞因子、趋化因子和/或生长因子的过度表达,导致增殖信号的积累,同时激活先天和选择性适应性免疫细胞。现在认为这种慢性炎症状态与诱导恶性转化、血管生成、转移、适应性免疫的颠覆以及治疗耐药性有关。此外,越来越多的证据表明 NF-κB 信号转导参与诱导和维持与上皮到间充质转化 (EMT) 和转移相关的浸润表型。在这篇综述中,我们总结了报道的 NF-κB 信号转导与上皮到间充质表型的连续转变步骤之间的联系。了解 NF-κB 在 EMT 调控中的作用可能有助于制定癌症的优化治疗策略。视频摘要。