Abballe Luana, Mastronuzzi Angela, Miele Evelina, Carai Andrea, Besharat Zein Mersini, Moretti Marta, De Smaele Enrico, Giangaspero Felice, Locatelli Franco, Ferretti Elisabetta, Po Agnese
Department of Experimental Medicine, Sapienza University, Rome, Italy.
Department of Pediatric Hematology/Oncology and Cellular and Gene Therapy, Bambino Gesù Children's Hospital, Rome, Italy.
Front Pediatr. 2018 Nov 1;6:315. doi: 10.3389/fped.2018.00315. eCollection 2018.
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.
Numb是一种具有多种功能的细胞内蛋白质。两种常见的异构体，Numb p66和Numb p72，是神经元发育中分化和增殖的调节因子。此外，Numb作为干细胞和癌症干细胞的细胞命运决定因素，其异常表达已在几种癌症中被描述。失调的Numb表达与儿童恶性脑肿瘤髓母细胞瘤有关，而这些肿瘤及其衍生的癌症干细胞样细胞中的Numb异构体，迄今为止尚未得到研究。在这里，我们表明髓母细胞瘤干细胞样细胞和小脑神经元干细胞（NSCs）表达Numb p66，其表达会影响干性特征。此外，本研究中评估的髓母细胞瘤样本与正常组织相比，Numb p66水平降低而Numb p72过表达。我们的结果揭示了在髓母细胞瘤中检测到的两种主要Numb异构体的不同作用，以及Numb p66在调节干细胞样细胞和NSCs维持中的关键作用。
