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 language | English |
|---|---|
| Article number | 315 |
| Journal | Frontiers in Pediatrics |
| Volume | 6 |
| DOIs | |
| Publication status | Published - Nov 1 2018 |
Fingerprint
Keywords
- Cancer stem cells
- Medulloblastoma
- Neural stem cells
- Numb
- NUMB isoforms
- Sonic hedgehog signaling
ASJC Scopus subject areas
- Pediatrics, Perinatology, and Child Health
Cite this
Numb isoforms deregulation in medulloblastoma and role of p66 isoform in cancer and neural stem cells. / Abballe, Luana; Mastronuzzi, Angela; Miele, Evelina; Carai, Andrea; Besharat, Zein Mersini; Moretti, Marta; De Smaele, Enrico; Giangaspero, Felice; Locatelli, Franco; Ferretti, Elisabetta; Po, Agnese.
In: Frontiers in Pediatrics, Vol. 6, 315, 01.11.2018.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Numb isoforms deregulation in medulloblastoma and role of p66 isoform in cancer and neural stem cells
AU - Abballe, Luana
AU - Mastronuzzi, Angela
AU - Miele, Evelina
AU - Carai, Andrea
AU - Besharat, Zein Mersini
AU - Moretti, Marta
AU - De Smaele, Enrico
AU - Giangaspero, Felice
AU - Locatelli, Franco
AU - Ferretti, Elisabetta
AU - Po, Agnese
PY - 2018/11/1
Y1 - 2018/11/1
N2 - 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.
AB - 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.
KW - Cancer stem cells
KW - Medulloblastoma
KW - Neural stem cells
KW - Numb
KW - NUMB isoforms
KW - Sonic hedgehog signaling
UR - http://www.scopus.com/inward/record.url?scp=85057200346&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85057200346&partnerID=8YFLogxK
U2 - 10.3389/fped.2018.00315
DO - 10.3389/fped.2018.00315
M3 - Article
AN - SCOPUS:85057200346
VL - 6
JO - Frontiers in Pediatrics
JF - Frontiers in Pediatrics
SN - 2296-2360
M1 - 315
ER -