Cellular prion protein controls stem cell-like properties of human glioblastoma tumor-initiating cells.
Cellular prion protein controls stem cell-like properties of human glioblastoma tumor-initiating cells.
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DOI：
10.18632/oncotarget.9575
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发表时间：
2016-06-21
期刊：
影响因子：
--
通讯作者：
Florio T
中科院分区：
文献类型：
--
作者：
Corsaro A;Bajetto A;Thellung S;Begani G;Villa V;Nizzari M;Pattarozzi A;Solari A;Gatti M;Pagano A;Würth R;Daga A;Barbieri F;Florio T
朊病毒蛋白（PrPC）是一种细胞表面糖蛋白，其错误折叠是导致朊病毒疾病的原因。尽管其生理作用尚未完全确定，但多项证据表明 PrPC 参与神经干细胞的自我更新、多能性基因表达、增殖和分化。 Moreover, PrPC regulates different biological functions in human tumors, including glioblastoma (GBM).我们分析了 PrPC 在 GBM 细胞致病性中的作用，重点关注肿瘤起始细胞（TIC 或癌症干细胞，CSC），该亚群负责大多数恶性肿瘤的发生、进展和复发。通过分析四种 GBM CSC 富集培养物，我们发现 PrPC 表达与细胞增殖率直接相关。为了更好地确定其在 CSC 生物学中的作用，我们通过特定的慢病毒传递的 shRNA 敲低了两种 GBM 衍生的 CSC 培养物中 PrPC 的表达。我们提供的证据表明，PrPC 下调的细胞中 CSC 增殖率、球形生成和体内致瘤性均受到显着抑制。此外，PrPC 下调导致干性和自我更新标记（NANOG、Sox2）表达丧失以及分化途径激活（即 GFAP 表达增加）。我们的结果表明，PrPC 控制人类 GBM CSC 的干性特性，并且其下调会诱导获得更具分化性和更少致癌性的表型。
Prion protein (PrPC) is a cell surface glycoprotein whose misfolding is responsible for prion diseases. Although its physiological role is not completely defined, several lines of evidence propose that PrPC is involved in self-renewal, pluripotency gene expression, proliferation and differentiation of neural stem cells. Moreover, PrPC regulates different biological functions in human tumors, including glioblastoma (GBM). We analyzed the role of PrPC in GBM cell pathogenicity focusing on tumor-initiating cells (TICs, or cancer stem cells, CSCs), the subpopulation responsible for development, progression and recurrence of most malignancies. Analyzing four GBM CSC-enriched cultures, we show that PrPC expression is directly correlated with the proliferation rate of the cells. To better define its role in CSC biology, we knocked-down PrPC expression in two of these GBM-derived CSC cultures by specific lentiviral-delivered shRNAs. We provide evidence that CSC proliferation rate, spherogenesis and in vivo tumorigenicity are significantly inhibited in PrPC down-regulated cells. Moreover, PrPC down-regulation caused loss of expression of the stemness and self-renewal markers (NANOG, Sox2) and the activation of differentiation pathways (i.e. increased GFAP expression). Our results suggest that PrPC controls the stemness properties of human GBM CSCs and that its down-regulation induces the acquisition of a more differentiated and less oncogenic phenotype.
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影响因子：
11.2
作者：
Adorno-Cruz V;Kibria G;Liu X;Doherty M;Junk DJ;Guan D;Hubert C;Venere M;Mulkearns-Hubert E;Sinyuk M;Alvarado A;Caplan AI;Rich J;Gerson SL;Lathia J;Liu H
通讯作者：
Liu H
影响因子：
25
作者：
Aguzzi, Adriano;Falsig, Jeppe
通讯作者：
Falsig, Jeppe
影响因子：
6.4
作者：
Du, JP;Pan, YL;Fan, DM
通讯作者：
Fan, DM
DOI：
10.1196/annals.1299.114
发表时间：
2003-01-01
期刊：
APOPTOSIS: FROM SIGNALING PATHWAYS TO THERAPEUTIC TOOLS
影响因子：
--
作者：
Corsaro, A;Thellung, S;Florio, T
通讯作者：
Florio, T
影响因子：
4.8
作者：
Barbieri, Federica;Pattarozzi, Alessandra;Florio, Tullio
通讯作者：
Florio, Tullio