Post-translational Modifications of OLIG2 Regulate Glioma Invasion through the TGF-β Pathway.

Abstract:

: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-β2 expression and promotes invasive mesenchymal properties in glioma cells. Inhibition of the TGF-β2 pathway blocks this OLIG2-dependent invasion. Furthermore, ectopic expression of phosphomimetic Olig2 is sufficient to block TGF-β2-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.

journal_name

Cell Rep

journal_title

Cell reports

authors

Singh SK,Fiorelli R,Kupp R,Rajan S,Szeto E,Lo Cascio C,Maire CL,Sun Y,Alberta JA,Eschbacher JM,Ligon KL,Berens ME,Sanai N,Mehta S

doi

10.1016/j.celrep.2016.06.045

subject

Has Abstract

pub_date

2016-07-26 00:00:00

pages

950-966

issue

4

issn

2211-1247

pii

S2211-1247(16)30799-9

journal_volume

16

pub_type

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