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

• Published in: Oncogene Vol. 33; no. 17; pp. 2236 - 2244
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 24.04.2014; Nature Publishing Group
• Subjects: 631/67/1922; 631/67/71; 692/420/755; Animals; Apoptosis; Brain cancer; Brain Neoplasms - genetics; Brain Neoplasms - metabolism; Brain Neoplasms - pathology; Brain tumors; Cancer; Carcinogenesis; Carcinogenesis - metabolism; Carrier Proteins - genetics; Carrier Proteins - metabolism; Cell Biology; Cell Proliferation; Cell self-renewal; Cytokines - genetics; Cytokines - metabolism; Development and progression; Gene Expression Regulation, Neoplastic; Genetic aspects; Glioblastoma; Glioblastoma - genetics; Glioblastoma - metabolism; Glioblastoma - pathology; Glioblastoma multiforme; HEK293 Cells; Human Genetics; Humans; Internal Medicine; Medicine; Medicine & Public Health; Mice; Mice, Inbred BALB C; Mice, Nude; Neoplasm Transplantation; Neoplastic Stem Cells - metabolism; Neoplastic Stem Cells - pathology; Neoplastic Stem Cells - physiology; Neural stem cells; Oncology; Oncology, Experimental; original-article; Phosphotransferases; Pleiotrophin; Progenitor cells; Properties; Protein-tyrosine kinase; Receptor Protein-Tyrosine Kinases - metabolism; SOXB1 Transcription Factors - metabolism; Stem cells; Transcriptional Activation; Tumor Cells, Cultured; Tumorigenesis; Tumorigenicity; Tumors; ALK; SOX2; kinase; pleiotrophin; glioblastoma; cancer stem cell
• ISSN: 0950-9232; 1476-5594
• DOI: 10.1038/onc.2013.168

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.