title: The pleiotrophin-ALK axis is required for tumorigenicity of glioblastoma stem cells.
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.
authors.affiliation: Laboratory of Molecular and Genetic Information, Institute of Molecular and Cellular Biosciences, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
authors.forename: R
authors.initials: R
authors.lastname: Koyama-Nasu
authors.affiliation: Laboratory of Molecular and Genetic Information, Institute of Molecular and Cellular Biosciences, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
authors.forename: R
authors.initials: R
authors.lastname: Haruta
authors.affiliation: Laboratory of Molecular and Genetic Information, Institute of Molecular and Cellular Biosciences, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Nasu-Nishimura
authors.affiliation: Laboratory of Molecular and Genetic Information, Institute of Molecular and Cellular Biosciences, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Taniue
authors.affiliation: Laboratory of Genome Structure and Function, Center for Epigenetic Disease, Institute of Molecular and Cellular Biosciences, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Katou
authors.affiliation: Laboratory of Genome Structure and Function, Center for Epigenetic Disease, Institute of Molecular and Cellular Biosciences, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Shirahige
authors.affiliation: Department of Neurosurgery, The University of Tokyo Hospital, Bunkyo-ku, Tokyo, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Todo
authors.affiliation: Department of Neurosurgery, The University of Tokyo Hospital, Bunkyo-ku, Tokyo, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Ino
authors.affiliation: Department of Neurosurgery, The University of Tokyo Hospital, Bunkyo-ku, Tokyo, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Mukasa
authors.affiliation: Department of Neurosurgery, The University of Tokyo Hospital, Bunkyo-ku, Tokyo, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Saito
authors.affiliation: Laboratory of Molecular and Genetic Information, Institute of Molecular and Cellular Biosciences, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Matsui
authors.affiliation: Laboratory of Molecular and Genetic Information, Institute of Molecular and Cellular Biosciences, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
authors.forename: R
authors.initials: R
authors.lastname: Takahashi
authors.affiliation: Laboratory of Molecular and Genetic Information, Institute of Molecular and Cellular Biosciences, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Hoshino-Okubo
authors.affiliation: Laboratory of Molecular and Genetic Information, Institute of Molecular and Cellular Biosciences, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Sugano
authors.affiliation: Laboratory of Molecular and Genetic Information, Institute of Molecular and Cellular Biosciences, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
authors.forename: E
authors.initials: E
authors.lastname: Manabe
authors.affiliation: Laboratory of Molecular and Genetic Information, Institute of Molecular and Cellular Biosciences, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Funato
authors.affiliation: Laboratory of Molecular and Genetic Information, Institute of Molecular and Cellular Biosciences, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Akiyama
mesh_terms: D000077548:Anaplastic Lymphoma Kinase; D000818:Animals; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D063646:Carcinogenesis / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D049109:Cell Proliferation; D016207:Cytokines / Q000235:genetics* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D005909:Glioblastoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology / Q000502:physiology; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D055748:SOXB1 Transcription Factors / Q000378:metabolism; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured
chemical_list: D002352:Carrier Proteins; D016207:Cytokines; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors; C066845:pleiotrophin; C000626173:ALK protein, human; C000626174:Alk protein, mouse; D000077548:Anaplastic Lymphoma Kinase; D020794:Receptor Protein-Tyrosine Kinases