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Proteomic Analysis Implicates Vimentin in Glioblastoma Cell Migration

Harvey W. Cushing Neurooncology Laboratories, Department of Neurosurgery, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA
Author to whom correspondence should be addressed.
Cancers 2019, 11(4), 466;
Received: 25 February 2019 / Revised: 22 March 2019 / Accepted: 29 March 2019 / Published: 3 April 2019
(This article belongs to the Special Issue Glioblastoma: State of the Art and Future Perspectives)
We previously showed lithium chloride (LiCl) and other inhibitors of glycogen synthase kinase-3 (GSK-3) including 6-bromo-indirubin-3-oxime (BIO), can block glioblastoma (GBM) cell migration. To investigate the mechanisms involved we used two-dimensional difference in-gel electrophoresis (2D-DIGE) and mass spectrometry to identify proteins altered after treatment of U251 GBM cells with 20 mM LiCl. Downregulation of the intermediate filament protein vimentin was the most significant change identified. Analysis of patient tumor samples revealed that vimentin is expressed abundantly in GBM, and is prognostic especially in lower grade tumors. Additionally, siRNA-mediated vimentin knockdown impaired GBM migration. Western blotting showed that treatment with LiCl or small molecule GSK-3 inhibitors led to the rapid downregulation of detergent soluble vimentin levels across a panel of GBM-derived cells. Fluorescence reactivation after photobleaching (FRAP) microscopy studies showed a significant reduction in the ability of the vimentin cytoskeleton to recover from photo-bleaching in the presence of LiCl or BIO. Biochemical studies revealed that GSK-3 and vimentin directly interact, and analysis of vimentin revealed a GSK-3 consensus phosphorylation site. We conclude that anti-migratory compounds with the ability to inhibit GSK-3 have effects on vimentin cytoskeletal dynamics, which may play a role in their anti-invasive activity. View Full-Text
Keywords: vimentin; GSK-3; glioblastoma; motility; cytoskeleton vimentin; GSK-3; glioblastoma; motility; cytoskeleton
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Nowicki, M.O.; Hayes, J.L.; Chiocca, E.A.; Lawler, S.E. Proteomic Analysis Implicates Vimentin in Glioblastoma Cell Migration. Cancers 2019, 11, 466.

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