AUTHOR=Abballe Luana , Mastronuzzi Angela , Miele Evelina , Carai Andrea , Besharat Zein Mersini , Moretti Marta , De Smaele Enrico , Giangaspero Felice , Locatelli Franco , Ferretti Elisabetta , Po Agnese TITLE=Numb Isoforms Deregulation in Medulloblastoma and Role of p66 Isoform in Cancer and Neural Stem Cells JOURNAL=Frontiers in Pediatrics VOLUME=6 YEAR=2018 URL=https://www.frontiersin.org/journals/pediatrics/articles/10.3389/fped.2018.00315 DOI=10.3389/fped.2018.00315 ISSN=2296-2360 ABSTRACT=

Numb is an intracellular protein with multiple functions. The two prevalent isoforms, Numb p66 and Numb p72, are regulators of differentiation and proliferation in neuronal development. Additionally, Numb functions as cell fate determinant of stem cells and cancer stem cells and its abnormal expression has been described in several types of cancer. Involvement of deregulated Numb expression has been described in the malignant childhood brain tumor medulloblastoma, while Numb isoforms in these tumors and in cancer stem-like cells derived from them, have not been studied to date. Here we show that medulloblastoma stem-like cells and cerebellar neuronal stem cells (NSCs) express Numb p66 where its expression tampers stemness features. Furthermore, medulloblastoma samples evaluated in this study express decreased levels of Numb p66 while overexpressed Numb p72 compared with normal tissues. Our results uncover different roles for the two major Numb isoforms examined in medulloblastoma and a critical role for Numb p66 in regulating stem-like cells and NSCs maintenance.