Institute of Cancer and Genomic Sciences, The University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK.
Health Research Institute, University of Limerick, Castletroy, Limerick, V94 T9PX, Ireland.
Oncogene. 2021 Nov;40(45):6321-6328. doi: 10.1038/s41388-021-02025-8. Epub 2021 Oct 8.
Induced waves of calcium fluxes initiate multiple signalling pathways that play an important role in the differentiation and maturation of B-cells. Finely tuned transient Ca fluxes from the endoplasmic reticulum in response to B-cell receptor (BCR) or chemokine receptor activation are followed by more sustained calcium influxes from the extracellular environment and contribute to the mechanisms responsible for the proliferation of B-cells, their migration within lymphoid organs and their differentiation. Dysregulation of these well-balanced mechanisms in B-cell lymphomas results in uncontrolled cell proliferation and resistance to apoptosis. Consequently, several cytotoxic drugs (and anti-proliferative compounds) used in standard chemotherapy regimens for the treatment of people with lymphoma target calcium-dependent pathways. Furthermore, ~10% of lymphoma associated mutations are found in genes with functions in calcium-dependent signalling, including those affecting B-cell receptor signalling pathways. In this review, we provide an overview of the Ca-dependent signalling network and outline the contribution of its key components to B cell lymphomagenesis. We also consider how the oncogenic Epstein-Barr virus, which is causally linked to the pathogenesis of a number of B-cell lymphomas, can modify Ca-dependent signalling.
诱导钙流波引发多种信号通路，这些信号通路在 B 细胞的分化和成熟中发挥重要作用。B 细胞受体 (BCR) 或趋化因子受体激活后，内质网中精细调节的瞬时 Ca 流随后是来自细胞外环境的更持续的钙内流，有助于增殖 B 细胞、在淋巴器官内迁移和分化的机制。B 细胞淋巴瘤中这些平衡良好的机制失调会导致不受控制的细胞增殖和抗凋亡。因此，标准化疗方案中用于治疗淋巴瘤患者的几种细胞毒性药物（和抗增殖化合物）靶向依赖钙的途径。此外，约 10%的淋巴瘤相关突变发生在钙依赖性信号转导功能的基因中，包括那些影响 B 细胞受体信号通路的基因。在这篇综述中，我们概述了 Ca 依赖性信号网络，并概述了其关键成分对 B 细胞淋巴瘤发生的贡献。我们还考虑了致癌性 Epstein-Barr 病毒如何修饰 Ca 依赖性信号转导，该病毒与多种 B 细胞淋巴瘤的发病机制有关。
