In glioblastoma, invasion and proliferation are presumed to be mutually exclusive events; however, the molecular mechanisms that mediate this switch at the cellular level remain elusive. Previously, we have shown that phospho-OLIG2, a central-nervous-system-specific transcription factor, is essential for tumor growth and proliferation. Here, we show that the modulation of OLIG2 phosphorylation can trigger a switch between proliferation and invasion. Glioma cells with unphosphorylated OLIG2S10, S13, S14 are highly migratory and invasive, both in vitro and in vivo. Mechanistically, unphosphorylated OLIG2 induces TGF-Î²2 expression and promotes invasive mesenchymal properties in glioma cells. Inhibition of the TGF-Î²2 pathway blocks this OLIG2-dependent invasion. Furthermore, ectopic expression of phosphomimetic Olig2 is sufficient to block TGF-Î²2-mediated invasion and reduce expression of invasion genes (ZEB1 and CD44). Our results not only provide a mechanistic insight into how cells switch from proliferation to invasion but also offer therapeutic opportunities for inhibiting dissemination of gliomas.
Digital Object Identifier (DOI)
Singh, Shiv K.; Fiorelli, Roberto; Kupp, Robert; Rajan, Sindhu; Szeto, Emily; Cascio, Costanza Lo; Maire, Cecile L.; Sun, Yu; Alberta, John A.; Eschbacher, Jennifer M.; Ligon, Keith L.; Berens, Michael E.; Sanai, Nader; and Mehta, Shwetal, "Post-Translational Modifications Of Olig2 Regulate Glioma Invasion Through The Tgf-Î² Pathway" (2016). Neurobiology. 300.