Numb Isoforms Deregulation in Medulloblastoma and Role of p66 Isoform in Cancer and Neural Stem Cells

被引：11
作者：
Abballe, Luana [1 ]
Mastronuzzi, Angela [2 ]
Miele, Evelina [2 ]
Carai, Andrea [3 ]
Besharat, Zein Mersini [1 ]
Moretti, Marta [4 ]
De Smaele, Enrico [1 ]
Giangaspero, Felice [5 ,6 ]
Locatelli, Franco [2 ,7 ]
Ferretti, Elisabetta [1 ,6 ]
Po, Agnese [4 ]
机构：
[1] Sapienza Univ, Dept Expt Med, Rome, Italy
[2] Bambino Gesu Pediat Hosp, Dept Pediat Hematol Oncol & Cellular & Gene Thera, Rome, Italy
[3] Bambino Gesu Pediat Hosp, Dept Neurosci & Neurorehabil, Neurosurg Unit, Rome, Italy
[4] Sapienza Univ, Dept Mol Med, Rome, Italy
[5] Sapienza Univ, Dept Radiol Oncol & Pathol Sci, Rome, Italy
[6] IRCCS Neuromed, Pozzilli, Italy
[7] Univ Pavia, Dept Paediat, Pavia, Italy
来源：
FRONTIERS IN PEDIATRICS | 2018年 / 6卷
关键词：
medulloblastoma; numb; NUMB isoforms; cancer stem cells; neural stem cells; sonic hedgehog signaling; HEPATOCELLULAR-CARCINOMA; CORTICAL NEUROGENESIS; MOUSE NUMB; FATE; SUPPRESSES; EXPRESSION; GROWTH; DIFFERENTIATION; IDENTIFICATION; DIVISION;
D O I：
10.3389/fped.2018.00315
中图分类号：
R72 [儿科学];
学科分类号：
100202 ;
摘要：
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.
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页数：10
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