Unexpected functions of nuclear factor-κB during germinal center B-cell development: implications for lymphomagenesis.
Unexpected functions of nuclear factor-κB during germinal center B-cell development: implications for lymphomagenesis.
复制标题
DOI：
10.1097/moh.0000000000000160
复制
发表时间：
2015-07
影响因子：
3.2
通讯作者：
Heise N
中科院分区：
文献类型：
--
作者：
Klein U;Heise N
源自生发中心 (GC) B 细胞转化的 B 细胞肿瘤经常含有基因突变，导致核因子 -κB (NF-κB) 信号通路的组成性激活。这篇综述重点介绍了对 GC B 细胞发育中单独的 NF-κB 转录因子的作用的最新见解，并讨论了这些结果对 GC 淋巴瘤发生的影响。了解异常 NF-κB 激活如何促进肿瘤发生需要了解 NF-κB 在肿瘤前体细胞中的作用。尽管人们对 NF-κB 生物学有了广泛的了解，但这种复杂的信号通路在 GC B 细胞分化中的功能在很大程度上尚不清楚。这篇综述将讨论最近的发现，这些发现揭示了在 GC 淋巴瘤发生过程中 GC 反应期间单独的 NF-κB 转录因子的不同作用。最值得注意的是，我们发现单个 NF-κB 亚基 c-REL 是维持 GC 反应所必需的，并且与促进细胞生长的代谢程序的激活有关。鉴定单独的 NF-κB 转录因子亚基在 GC 生物学中的生物学作用将有助于更好地了解它们在 B 细胞肿瘤中组成性激活的致病后果。这一知识可用于开发靶向抗肿瘤疗法，旨在选择性抑制有助于发病机制的异常 NF-κB 活性成分。
B-cell tumors originating from the transformation of germinal center (GC) B-cells frequently harbor genetic mutations leading to constitutive activation of the nuclear factor-κB (NF-κB) signaling pathway. This review highlights recent insights into the roles of separate NF-κB transcription factors in GC B-cell development and discusses implications of the results for GC-lymphomagenesis. Understanding how aberrant NF-κB-activation promotes tumorigenesis requires the understanding of the role of NF-κB in the tumor-precursor cells. Despite extensive knowledge on NF-κB biology, the function of this complex signaling pathway in the differentiation of GC B-cells is largely unknown. This review will discuss recent findings that revealed distinct roles of separate NF-κB transcription factors during the GC-reaction in the context of GC-lymphomagenesis. Most notably, a single NF-κB subunit, c-REL, was found to be required for the maintenance of the GC-reaction and was associated with the activation of a metabolic program that promotes cell growth. Identifying the biological roles of the separate NF-κB transcription factor subunits in GC-biology will help to better understand the pathogenic consequences of their constitutive activation in B-cell tumors. This knowledge may be exploited for the development of targeted anti-tumor therapies aimed at inhibiting selectively those components of aberrant NF-κB activity which contribute to pathogenesis.