TUBB2B通过与波形蛋白相互作用调节上皮-间质转化，以促进胶质瘤的迁移和侵袭。

TUBB2B regulates epithelial-mesenchymal transition via interaction with Vimentin to promote glioma migration and invasion.

作者信息

Li Junxi, Zhou Zhengjun, Zhang Junrong, Wang Ming, Luan Xingzhao, Zhao Mingkuan, Jiang Geng, Wang Guiyuan, Li Shenjie, Xiang Wei, Chen Ligang, Zhou Jie

机构信息

Department of Neurosurgery, The Affiliated Hospital, Southwest Medical University, 25 Taiping Street, Luzhou, Sichuan, 646000, China.

Department of Neurosurgery, Yibin No.4 People's Hospital, Yibin, Sichuan, China.

出版信息

Cancer Cell Int. 2024 Dec 20;24(1):423. doi: 10.1186/s12935-024-03618-5.

DOI:10.1186/s12935-024-03618-5

PMID:39707368

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11662515/

Abstract

BACKGROUND

Epithelial-mesenchymal transition (EMT) plays a crucial role in the migration and invasion capabilities of glioblastoma (GBM) cells. Several studies have established tubulin as a significant regulator of the EMT process. Tubulin beta 2B class IIb (TUBB2B), a critical component of microtubules, has been linked to the prognosis of various tumors. However, the specific biological function and mechanism of TUBB2B in GBM remain unclear.

METHODS

In vitro experiments demonstrated that TUBB2B knockdown inhibited the migration and invasion of GBM cells, while its overexpression enhanced these capabilities. Western blot, immunofluorescence (IF) and co-immunoprecipitation (Co-IP) assays revealed that TUBB2B interacts with Vimentin. Molecular docking and residue mutation scanning indicated that TUBB2B interacts with Vimentin at the R391/K392/A393/F394 sites. In vivo experiments using nude mice confirmed that TUBB2B knockdown inhibited GBM cell invasion and migration.

RESULTS

TUBB2B was upregulated in GBM tissue samples compared with normal tissues. The sites of TUBB2B(R391/K392/A393/F394) physically interacts with Vimentin to induce EMT, which promotes migration and invasion.

CONCLUSION

TUBB2B may regulate EMT and promote the migration and invasion of GBM cells through its interaction with Vimentin, highlighting TUBB2B as a potential therapeutic target for GBM.

摘要

背景

上皮-间质转化（EMT）在胶质母细胞瘤（GBM）细胞的迁移和侵袭能力中起关键作用。多项研究已证实微管蛋白是EMT过程的重要调节因子。微管蛋白β2B IIb类（TUBB2B）作为微管的关键组成部分，与多种肿瘤的预后相关。然而，TUBB2B在GBM中的具体生物学功能和机制仍不清楚。

方法

体外实验表明，敲低TUBB2B可抑制GBM细胞的迁移和侵袭，而过表达则增强这些能力。蛋白质免疫印迹、免疫荧光（IF）和免疫共沉淀（Co-IP）分析显示，TUBB2B与波形蛋白相互作用。分子对接和残基突变扫描表明，TUBB2B在R391/K392/A393/F394位点与波形蛋白相互作用。使用裸鼠进行的体内实验证实，敲低TUBB2B可抑制GBM细胞的侵袭和迁移。