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

The invasive nature of glioblastoma is one important reason of treatment failure. Glioblastoma 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 knock-down impairs progenitor migration to the olfactory bulb. Its expression is retained in glioblastoma 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.