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

Risultato della ricerca: Contributo in rivistaArticolo in rivista

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.
Lingua originaleEnglish
pagine (da-a)1-10
Numero di pagine10
RivistaFrontiers in Pediatrics
Volume6
DOI
Stato di pubblicazionePubblicato - 2018

Keywords

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

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