Wang Yan, Zhang Yu, Sang Ben, Zhu Xianlong, Yu Rutong, Zhou Xiuping
The Graduate School, Xuzhou Medical University, Xuzhou, Jiangsu 221002, P.R. China.
Institute of Nervous System Diseases, Xuzhou Medical University, Xuzhou, Jiangsu 221002, P.R. China.
Oncol Lett. 2021 Feb;21(2):167. doi: 10.3892/ol.2021.12428. Epub 2021 Jan 4.
Human giant larvae-1 (Hugl-1) is a human homologue of tumor suppressor lethal (2)-giant larvae and has been reported to be involved in the development of human malignancies. Previous studies performed by our group demonstrated that Hugl-1 inhibits glioma cell proliferation in an intracranial model of nude mice. However, the exact molecular mechanisms underlying the participation of Hugl-1 in glioma invasion and migration, and in the depolarizing process remain largely unknown. Utilizing the U251-MG cells with stable expression of Hugl-1, the present study used wound healing, Transwell invasion and western blot assays to explore the role and specific mechanism of Hugl-1 in glioma invasion and migration. The results of the present study demonstrated that overexpression of Hugl-1 decreased cell-cell adhesion and increased cell-cell extracellular matrix adhesion. In addition, overexpression of Hugl-1 promoted pseudopodia formation, glioma cell migration and invasion. The molecular mechanism of action involved the negative regulation of N-cadherin protein levels by Hugl-1. Overexpression or knockdown of N-cadherin partially suppressed or enhanced the effects of Hugl-1 on glioma cell migration and invasion, respectively. Furthermore, Hugl-1 inhibited cell proliferation, while promoting cell migration, which suggests that it may serve a two-sided biological role in cellular processes. Taken together, these results suggest that Hugl-1 promotes the migration and invasion of malignant glioma cells by decreasing N-cadherin expression. Thus, Hugl-1 may be applied in the development of targeted and personalized treatment.
人类巨大幼虫-1（Hugl-1）是肿瘤抑制因子致死（2）-巨大幼虫的人类同源物，据报道其参与人类恶性肿瘤的发生发展。我们团队之前进行的研究表明，Hugl-1在裸鼠颅内模型中抑制胶质瘤细胞增殖。然而，Hugl-1参与胶质瘤侵袭、迁移以及去极化过程的确切分子机制仍 largely unknown。本研究利用稳定表达Hugl-1的U251-MG细胞，采用伤口愈合实验、Transwell侵袭实验和蛋白质免疫印迹法，探究Hugl-1在胶质瘤侵袭和迁移中的作用及具体机制。本研究结果表明，Hugl-1的过表达降低了细胞间黏附，增加了细胞与细胞外基质的黏附。此外，Hugl-1的过表达促进了伪足形成、胶质瘤细胞迁移和侵袭。其作用的分子机制涉及Hugl-1对N-钙黏蛋白蛋白水平的负调控。N-钙黏蛋白的过表达或敲低分别部分抑制或增强了Hugl-1对胶质瘤细胞迁移和侵袭的影响。此外，Hugl-1抑制细胞增殖，同时促进细胞迁移，这表明它可能在细胞过程中发挥双向生物学作用。综上所述，这些结果表明Hugl-1通过降低N-钙黏蛋白的表达促进恶性胶质瘤细胞的迁移和侵袭。因此，Hugl-1可能应用于靶向和个性化治疗的开发。
