PDF(Pubmed)
Abstract：
In the early 1990\'s a group of unrelated genes were identified from the sites of recurring translocations in B-cell lymphomas. Despite sharing the nomenclature \'Bcl\', and an association with blood-borne cancer, these genes have unrelated functions. Of these genes, BCL2 is best known as a key cancer target involved in the regulation of caspases and other cell viability mechanisms. BCL3 on the other hand was originally identified as a non-canonical regulator of NF-kB transcription factor pathways - a signaling mechanism associated with important cell outcomes including many of the hallmarks of cancer. Most of the early investigations into BCL3 function have since focused on its role in NF-kB mediated cell proliferation, inflammation/immunity and cancer. However, recent evidence is coming to light that this protein directly interacts with and modulates a number of other signaling pathways including DNA damage repair, WNT/β-catenin, AKT, TGFβ/SMAD3 and STAT3 - all of which have key roles in cancer development, metastatic progression and treatment of solid tumours. Here we review the direct evidence demonstrating BCL3\'s central role in a transcriptional network of signaling pathways that modulate cancer biology and treatment response in a range of solid tumour types and propose common mechanisms of action of BCL3 which may be exploited in the future to target its oncogenic effects for patient benefit.
摘要：
在1990年代初期，从B细胞淋巴瘤中反复易位的位点鉴定出一组不相关的基因。尽管共享术语\'Bcl\'，与血源性癌症有关，这些基因有不相关的功能。在这些基因中，BCL2被认为是参与胱天蛋白酶和其他细胞生存力机制调节的关键癌症靶标。另一方面，BCL3最初被鉴定为NF-kB转录因子途径的非规范调节因子-一种与重要细胞结果相关的信号机制，包括许多癌症标志。大多数对BCL3功能的早期研究都集中在其在NF-kB介导的细胞增殖中的作用。炎症/免疫和癌症。然而,最近的证据表明，这种蛋白质直接与许多其他信号通路相互作用并调节，包括DNA损伤修复，WNT/β-连环蛋白，AKT,TGFβ/SMAD3和STAT3-所有这些在癌症发展中起关键作用，实体瘤的转移性进展和治疗。在这里，我们回顾了证明BCL3在一系列实体瘤类型中调节癌症生物学和治疗反应的信号通路转录网络中的核心作用的直接证据，并提出了BCL3的共同作用机制，这些机制可能在未来被利用来靶向其致癌效应，以使患者受益。
