FCCC LOGO Faculty Publications
Wang Q , Wu H , Hu J , Fu H , Qu Y , Yang Y , Cai Q , Efimov A , Wu M , Yen T , Wang Y , Yang ZJ
Nestin is required for spindle assembly and cell cycle progression in glioblastoma cells
Mol Cancer Res. 2021 Oct;19(10) :1651-1665
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Abstract
Nestin, a class IV intermediate filament protein, is generally considered as a putative marker of neural stem and progenitor cells in the central nervous system. Glioma is a common type of adult brain tumors, and glioblastoma (GBM) represents the most aggressive form of glioma. Here, we report that Nestin expression is significantly up-regulated in human GBM, compared with other types of glioma. Nestin knockdown or deletion in U251 cells and tumor cells from GBM patients derived xenografts (PDX), resulted in G2/M arrest, finally leading to apoptosis in tumor cells. Using proximity-dependent Biotin identification method, we identified βII-tubulin as an interacting protein of Nestin in U251 cells. Nestin stabilized βII-tubulin in U251 cells through physical interaction. Knockdown of Nestin or βII-tubulin disrupted spindle morphology in tumor cells. Our studies further revealed that Nestin deficiency in U251 cells and GBM PDX cells repressed tumor growth upon transplantation. Finally, we found that Nestin deficiency sensitized GBM cells to microtubule-destabilizing drugs such as vinblastine and vincristine. Our studies demonstrate the essential functions and underlying mechanisms of Nestin in the growth and drug response of GBM cells. Implications: Through interaction with βII-tubulin, Nestin facilitates cell cycle progression and spindle assembly of tumor cells in glioblastoma.
Notes
1557-3125 Yang, Zeng-Jie Wang, Qinglin Wu, Hao Hu, Jian Fu, Haijuan Qu, Yanghui Yang, Yijun Cai, Qi Efimov, Andrey Wu, Minghua Yen, Tim Wang, Yuan Journal Article United States Mol Cancer Res. 2021 Jun 22:molcanres.0994.2020. doi: 10.1158/1541-7786.MCR-20-0994.