Journal
CELL REPORTS
Volume 16, Issue 4, Pages 950-966Publisher
CELL PRESS
DOI: 10.1016/j.celrep.2016.06.045
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Funding
- Arizona Biomedical Research Commission
- Barrow Neurological Foundation
- NIH/NINDS grant [R01 NS088648A]
- Bear Necessities Pediatric Cancer Foundation
- NIH [R01 NS082745, R01 CA175391]
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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 OLIG2 (S10, S13, S14) are highly migratory and invasive, both in vitro and in vivo. Mechanistically, unphosphorylated OLIG2 induces TGF-beta 2 expression and promotes invasive mesenchymal properties in glioma cells. Inhibition of the TGF-beta 2 pathway blocks this OLIG2-dependent invasion. Furthermore, ectopic expression of phosphomimetic Olig2 is sufficient to block TGF-beta 2-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.
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