Mesenchymal high-grade glioma is maintained by the ID-RAP-1 axis
文献类型：期刊论文
| 作者 | Niola F1; Zhao XD1; Singh D1; Sullivan R1; Castano A1; Verrico A1; Zoppoli P1; Friedmann-Morvinski D2; Sulman E3; Barrett L4 |
| 刊名 | JOURNAL OF CLINICAL INVESTIGATION
 |
| 出版日期 | 2013 |
| 卷号 | 123期号:1页码:405-417 |
| 通讯作者 | ai2102@colum-bia.edu |
| 合作状况 | 其它 |
| 英文摘要 | High-grade gliomas (HGGs) are incurable brain tumors that are characterized by the presence of glioma-inidating cells (GICs). GICs are essential to tumor aggressiveness and retain the capacity for self-renewal and multilineage differentiation as long as they reside in the perivascular niche. ID proteins are master regulators of stemness and anchorage to the extracellular niche microenvironment, suggesting that they may play a role in maintaining GICs. Here, we modeled the probable therapeutic impact of ID inactivation in HGG by selective ablation of Id in tumor cells and after tumor initiation in a new mouse model of human mesenchymal HGG. Deletion of 3 Id genes induced rapid release of GICs from the perivascular niche, followed by tumor regression. GIC displacement was mediated by derepression of Rap1gap and subsequent inhibition of RAP1, a master regulator of cell adhesion. We identified a signature module of 5 genes in the ID pathway, including RAP1GAP, which segregated 2 subgroups of glioma patients with markedly different clinical outcomes. The model-informed survival analysis together with genetic and functional studies establish that ID activity is required for the maintenance of mesenchymal HGG and suggest that pharmacological inactivation of ID proteins could serve as a therapeutic strategy. |
| 收录类别 | SCI |
| 资助信息 | This work was sup- ported by National Cancer Institute grants R01CA101644 and R01CA131126 (to A. Lasorella) and R01CA085628 and R01CA127643 (to A. Iavarone) and National Institute of Neuro- logical Disorders and Stroke grant R01NS061776 (to A. Iavarone). F. Niola and P. Zoppoli are supported by a fellowship from the Italian Ministry of Welfare/Provincia di Benevento. A. Verrico is a visiting scientist from the Department of Pediatrics, University Federico II, Naples, Italy. |
| 语种 | 英语 |
| 公开日期 | 2014-07-07 |
| 源URL | [http://159.226.149.42:8088/handle/152453/7943]  |
| 专题 | 昆明动物研究所_科研共享资源 |
| 作者单位 | 1.Institute for Cancer Genetics, Columbia University Medical Center, New York, New York, USA 2.Laboratory of Genetics, Salk Institute for Biological Studies, La Jolla, California, USA. 3.Department of Pathology, MD Anderson Cancer Center, Houston, Texas, USA 4.Cancer Biology and Genetics Program, Memorial Sloan-Kettering Cancer Center, New York, New York, USA 5.Department of Immunology, Duke University Medical Center, Durham, North Carolina, USA 6.Department of Neurology, Columbia University Medical Center, New York, New York, USA 7.Department of Pathology, Columbia University Medical Center, New York, New York, USA 8.Department of Pediatrics, Columbia University Medical Center, New York, New York, USA |
| 推荐引用方式 GB/T 7714 | Niola F,Zhao XD,Singh D,et al. Mesenchymal high-grade glioma is maintained by the ID-RAP-1 axis[J]. JOURNAL OF CLINICAL INVESTIGATION,2013,123(1):405-417. |
| APA | Niola F.,Zhao XD.,Singh D.,Sullivan R.,Castano A.,...&Lasorella A.(2013).Mesenchymal high-grade glioma is maintained by the ID-RAP-1 axis.JOURNAL OF CLINICAL INVESTIGATION,123(1),405-417. |
| MLA | Niola F,et al."Mesenchymal high-grade glioma is maintained by the ID-RAP-1 axis".JOURNAL OF CLINICAL INVESTIGATION 123.1(2013):405-417. |
入库方式： OAI收割
来源：昆明动物研究所
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