Wang Q, Wu H, Hu J, Fu H, Qu Y, Yang Y, Cai KQ, Efimov A, Wu M, Yen T, Wang Y, Yang ZJ

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 ...

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is significantly upregulated in human GBM, compared with other types of glioma. Nestin knockdown or deletion in U251 cells and tumor cells from GBM patients derived xenografts resulted in G2-M arrest, finally leading to apoptosis in tumor cells. Using proximity-dependent biotin identification method, we identified ?II-tubulin as an interacting protein of Nestin in U251 cells. Nestin stabilized ?II-tubulin in U251 cells through physical interaction. Knockdown of Nestin or ?II-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 ?II-tubulin, Nestin facilitates cell-cycle progression and spindle assembly of tumor cells in glioblastoma.

Date: Oct. 01, 2021

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