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The pleiotrophin-ALK axis is required for tumorigenicity of glioblastoma stem cells

Oncogene volume 33, pages 2236–2244 (2014)Cite this article

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Abstract

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.

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Acknowledgements

This work was supported by the Research Program of Innovative Cell Biology by Innovative Technology (Integrated Systems Analysis of Cellular Oncogenic Signaling Networks), Grants-in-Aid for Scientific Research on Innovative Areas (Integrative Research on Cancer Microenvironment Network), Takeda Science Foundation and, in part, by Global COE Program (Integrative Life Science Based on the Study of Biosignaling Mechanisms), MEXT, Japan.

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Authors and Affiliations

  1. Laboratory of Molecular and Genetic Information, Institute of Molecular and Cellular Biosciences, The University of Tokyo, Bunkyo-ku, Tokyo, Japan

    R Koyama-Nasu, R Haruta, Y Nasu-Nishimura, K Taniue, M Matsui, R Takahashi, A Hoshino-Okubo, H Sugano, E Manabe, K Funato & T Akiyama

  2. Laboratory of Genome Structure and Function, Center for Epigenetic Disease, Institute of Molecular and Cellular Biosciences, The University of Tokyo, Bunkyo-ku, Tokyo, Japan

    Y Katou & K Shirahige

  3. Department of Neurosurgery, The University of Tokyo Hospital, Bunkyo-ku, Tokyo, Japan

    T Todo, Y Ino, A Mukasa & N Saito

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Correspondence to T Akiyama.

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Koyama-Nasu, R., Haruta, R., Nasu-Nishimura, Y. et al. The pleiotrophin-ALK axis is required for tumorigenicity of glioblastoma stem cells. Oncogene 33, 2236–2244 (2014). https://doi.org/10.1038/onc.2013.168

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