Department II of Neurosurgery, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China.
Pediatric Department, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China.
Bioengineered. 2022 Feb;13(2):2207-2216. doi: 10.1080/21655979.2021.2023985.
DNA topoisomerase II alpha (TOP2A) reportedly plays a crucial role in several cancers, however, the precise regulatory role of TOP2A in metastatic characteristics of glioma is still poorly understood. Herein, we sought to elucidate the mechanisms by which TOP2A affects the metastatic phenotypes of glioma. We observed that a high level of TOP2A expression was dramatically linked with inferior survival in glioma patients while silencing of TOP2A impaired glioma cell proliferation and aggressiveness. TOP2A was found to directly interact with β-catenin and facilitated its translocation into the nucleus. Mechanistically, TOP2A effectively induced glioma cell growth and invasion in a β-catenin-dependent manner. Overall, we pinpoint TOP2A as a critical activator of the Wnt/β-catenin pathway in glioma, promoting cell growth, migration, and invasion.
DNA 拓扑异构酶 IIα（TOP2A）据报道在多种癌症中发挥着关键作用，然而，TOP2A 在神经胶质瘤转移特征中的精确调节作用仍知之甚少。在此，我们试图阐明 TOP2A 影响神经胶质瘤转移表型的机制。我们观察到 TOP2A 的高水平表达与神经胶质瘤患者的不良生存显著相关，而 TOP2A 的沉默则削弱了神经胶质瘤细胞的增殖和侵袭能力。发现 TOP2A 可直接与 β-连环蛋白相互作用，并促进其转位入核。从机制上讲，TOP2A 可有效地以 β-连环蛋白依赖的方式诱导神经胶质瘤细胞的生长和侵袭。总的来说，我们确定 TOP2A 是神经胶质瘤中 Wnt/β-连环蛋白通路的关键激活剂，促进细胞生长、迁移和侵袭。
