Rai is a new regulator of neural progenitor migration and glioblastoma invasion.
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.
Department of Experimental Oncology, European Institute of Oncology, Milan, Italy.
Barbara
B
Ortensi
Daniela
D
Osti
Serena
S
Pellegatta
Federica
F
Pisati
Paola
P
Brescia
Lorenzo
L
Fornasari
Daniel
D
Levi
Paolo
P
Gaetani
Piergiuseppe
P
Colombo
Anna
A
Ferri
Silvia
S
Nicolis
Gaetano
G
Finocchiaro
Giuliana
G
Pelicci
D000818:Animals; D002465:Cell Movement; D002470:Cell Survival; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D005909:Glioblastoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D058953:Neural Stem Cells / Q000378:metabolism* / Q000473:pathology; D009830:Olfactory Bulb; D055765:Shc Signaling Adaptor Proteins / Q000235:genetics / Q000378:metabolism*; D000071427:Src Homology 2 Domain-Containing, Transforming Protein 3; D014407:Tumor Cells, Cultured
D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; C122029:SHC3 protein, human; D055765:Shc Signaling Adaptor Proteins; C485682:Shc3 protein, mouse; D000071427:Src Homology 2 Domain-Containing, Transforming Protein 3