title: Glioma-initiating cells and molecular pathology: implications for therapy.
abstract: There is now compelling evidence that gliomas harbor a small population of cells, termed glioma-initiating cells (GICs), characterized by their ability to undergo self-renewal and initiate tumorigenesis. The development of therapeutic strategies targeted toward GIC signaling may improve the treatment of malignant gliomas. The characterization of GICs provides a clue to elucidating histological heterogeneity and treatment failure. The role of the stem cell marker CD133 in the initiation and progression of brain tumors is still uncertain. Here, we review some of the signaling mechanisms involved in GIC biology, such as phosphatase and tensin homolog (PTEN), sonic hedgehog, Notch, and WNT signaling pathways, maternal embryonic leucine-zipper kinase (MELK), BMI1, and Janus kinase signal transducer and activator of transcription (JAK-STAT) signaling. In addition, we discuss the role of microRNAs in GICs by focusing on microRNA-21 regulation by type I interferon.
authors.affiliation: Department of Neurosurgery, Nagoya University School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Natsume
authors.forename: Sayano
authors.initials: S
authors.lastname: Kinjo
authors.forename: Kanako
authors.initials: K
authors.lastname: Yuki
authors.forename: Takenori
authors.initials: T
authors.lastname: Kato
authors.forename: Masasuke
authors.initials: M
authors.lastname: Ohno
authors.forename: Kazuya
authors.initials: K
authors.lastname: Motomura
authors.forename: Kenichiro
authors.initials: K
authors.lastname: Iwami
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Wakabayashi
mesh_terms: D000071916:AC133 Antigen; D015703:Antigens, CD / Q000502:physiology*; D001932:Brain Neoplasms / Q000473:pathology* / Q000628:therapy*; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D018450:Disease Progression; D005910:Glioma / Q000473:pathology* / Q000628:therapy*; D006023:Glycoproteins / Q000502:physiology*; D053823:Hedgehog Proteins / Q000502:physiology; D006801:Humans; D035683:MicroRNAs / Q000502:physiology; D058990:Molecular Targeted Therapy; D009687:Nuclear Proteins / Q000502:physiology; D051059:PTEN Phosphohydrolase / Q000502:physiology*; D010455:Peptides / Q000502:physiology*; D063150:Polycomb Repressive Complex 1; D017346:Protein Serine-Threonine Kinases / Q000502:physiology; D011518:Proto-Oncogene Proteins / Q000502:physiology; D012097:Repressor Proteins / Q000502:physiology; D050796:STAT3 Transcription Factor / Q000502:physiology; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*; D051153:Wnt Proteins / Q000502:physiology
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; C069077:BMI1 protein, human; D006023:Glycoproteins; D053823:Hedgehog Proteins; D035683:MicroRNAs; D009687:Nuclear Proteins; C000606023:PROM1 protein, human; D010455:Peptides; D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins; C509239:SHH protein, human; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D051153:Wnt Proteins; D063150:Polycomb Repressive Complex 1; C484610:MELK protein, human; D017346:Protein Serine-Threonine Kinases; D051059:PTEN Phosphohydrolase