Numb isoforms deregulation in medulloblastoma and role of p66 isoform in cancer and neural stem cells

Luana Abballe, Angela Mastronuzzi, Evelina Miele, Andrea Carai, Zein Mersini Besharat, Marta Moretti, Enrico De Smaele, Felice Giangaspero, Franco Locatelli, Elisabetta Ferretti, Agnese Po

Research output: Contribution to journalArticle

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.

Original languageEnglish
Article number315
JournalFrontiers in Pediatrics
Volume6
DOIs
Publication statusPublished - Nov 1 2018

Keywords

  • Cancer stem cells
  • Medulloblastoma
  • Neural stem cells
  • Numb
  • NUMB isoforms
  • Sonic hedgehog signaling

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

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