Rai is a New Regulator of Neural Progenitor Migration and Glioblastoma Invasion§

Authors


  • Author contributions: B.O. and D.O.: conception and design, data collection and/or assembly, data analysis and interpretation, manuscript writing; S.P. and G.F.: data analysis and interpretation; F.P. and P.B.: data collection and/or assembly and data analysis and interpretation; L.F.: statistical analysis; D.L. and P.G.: GBM provision; P.C. and A.F.: data collection; S.N.: data interpretation; G.P.: conception and design, data analysis and interpretation, manuscript writing, and final approval of manuscript. B.O. and D.O. contributed equally to this article.

  • Disclosure of potential conflicts of interest is found at the end of this article.

  • §

    First published online in STEM CELLSEXPRESS February 6, 2012.

Abstract

The invasive nature of glioblastoma (GBM) is one important reason for treatment failure. GBM stem/progenitor cells retain the migratory ability of normal neural stem/progenitor cells and infiltrate the brain parenchyma. Here, we identify Rai (ShcC/N-Shc), a member of the family of Shc-like adaptor proteins, as a new regulator of migration of normal and cancer stem/progenitor cells. Rai is expressed in neurogenic areas of the brain and its knockdown impairs progenitor migration to the olfactory bulb. Its expression is retained in GBM stem/progenitor cells where it exerts the same promigratory activity. Rai silencing in cancer stem/progenitor cells isolated from different patients causes significant decrease in cell migration and invasion, both in vitro and in vivo, providing survival benefit. Rai depletion is associated with alteration of multiple-signaling pathways, yet it always leads to reduced expression of proinvasive genes. STEM CELLS 2012;30:817–832

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