Koyama-Nasu R, Haruta R, Nasu-Nishimura Y, Taniue K, Katou Y, Shirahige K, Todo T, Ino Y, Mukasa A, Saito N, Matsui M, Takahashi R, Hoshino-Okubo A, Sugano H, Manabe E, Funato K, Akiyama T
Laboratory of Molecular and Genetic Information, Institute of Molecular and Cellular Biosciences, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
Laboratory of Genome Structure and Function, Center for Epigenetic Disease, Institute of Molecular and Cellular Biosciences, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
Oncogene. 2014 Apr 24;33(17):2236-44. doi: 10.1038/onc.2013.168. Epub 2013 May 20.
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.
越来越多的证据表明，脑肿瘤起源于神经干/前体/祖细胞的转化。目前许多关于人类脑肿瘤的研究都集中在胶质母细胞瘤的干细胞样特性上。在此我们表明，间变性淋巴瘤激酶（ALK）及其配体多效生长因子对于胶质母细胞瘤干细胞（GSCs）的自我更新和致瘤性是必需的。此外，我们证明多效生长因子直接由SOX2反式激活，SOX2是维持神经干细胞和GSCs所必需的一种转录因子。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前景的靶点。
