The pleiotrophin-ALK axis is required for tumorigenicity of glioblastoma stem cells
The pleiotrophin-ALK axis is required for tumorigenicity of glioblastoma stem cells
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DOI：
10.1038/onc.2013.168
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发表时间：
2014-04-24
期刊：
影响因子：
8
通讯作者：
Akiyama, T.
中科院分区：
文献类型：
--
作者：
Koyama-Nasu, R.;Haruta, R.;Akiyama, T.
越来越多的证据表明，脑肿瘤源于神经干细胞/前体细胞/祖细胞的转化。目前对人类脑肿瘤的许多研究都集中在胶质母细胞瘤的干细胞样特性上。在这里，我们表明，间变性淋巴瘤激酶（ALK）和它的配体多效生长因子的自我更新和成胶质细胞瘤干细胞（GSC）的致瘤性所需的。此外，我们证明了多效生长因子是由SOX 2直接反式激活的，SOX 2是维持神经干细胞和GSC所必需的转录因子。我们推测多效生长因子-ALK轴可能是胶质母细胞瘤治疗的一个有希望的靶点。
Increasing evidence suggests that brain tumors arise from the transformation of neural stem/precursor/progenitor cells. Much current research on human brain tumors is focused on the stem-like properties of glioblastoma. Here we show that anaplastic lymphoma kinase (ALK) and its ligand pleiotrophin are required for the self-renewal and tumorigenicity of glioblastoma stem cells (GSCs). Furthermore, we demonstrate that pleiotrophin is transactivated directly by SOX2, a transcription factor essential for the maintenance of both neural stem cells and GSCs. We speculate that the pleiotrophin-ALK axis may be a promising target for the therapy of glioblastoma.