Department of Medical Oncology, Faculty of Medicine, University of Thessaly, University Hospital of Larissa, Biopolis, 41110, Larissa, Greece,
J Cell Commun Signal. 2013 Dec;7(4):235-7. doi: 10.1007/s12079-013-0198-2. Epub 2013 Mar 15.
Angiogenesis is an essential process for sustaining tumor growth, particularly in cancer cell types with rapid proliferation, including malignant glioma. Bmi-1 is a transcriptional regulator of the polycomb group involved in repression of gene expression by altering the state of chromatin at specific promoters. Bmi-1 overexpression was previously implicated in glioma tumorigenesis, proliferation, self-renewal, apoptotic resistance and invasiveness. In a recent study, Jiang et al. (PLoS One 8:e55527, 2013) have revealed the involvement of Bmi-1/NF-κB/VEGF pathway in promoting glioma cell-mediated tubule formation and migration of endothelial cells and neovascularization both in vitro and in vivo. NF-κB inhibition reversed these effects, supporting a role for Bmi-1 in glioma angiogenesis. Given the intimate association of Bmi-1 and NF-κB with the ubiquitin-proteasome system, a better understanding of protein turnover in angiogenic signaling, discussed here, provides novel implications for anti-angiogenic treatment strategies in gliomas.
血管生成是维持肿瘤生长的必要过程，特别是在增殖迅速的肿瘤细胞类型中，包括恶性神经胶质瘤。Bmi-1 是多梳组的转录调节因子，通过改变特定启动子处染色质的状态来抑制基因表达。Bmi-1 的过表达先前被认为与神经胶质瘤的肿瘤发生、增殖、自我更新、抗凋亡和侵袭有关。在最近的一项研究中，Jiang 等人（PLoS One 8:e55527, 2013）揭示了 Bmi-1/NF-κB/VEGF 通路在促进神经胶质瘤细胞介导的管腔形成和内皮细胞迁移以及体内外血管生成中的作用。NF-κB 抑制逆转了这些作用，支持 Bmi-1 在神经胶质瘤血管生成中的作用。鉴于 Bmi-1 和 NF-κB 与泛素-蛋白酶体系统的密切关联，本文讨论了对血管生成信号转导中蛋白质周转的更好理解，为神经胶质瘤的抗血管生成治疗策略提供了新的意义。
