title: Ceacam1L Modulates STAT3 Signaling to Control the Proliferation of Glioblastoma-Initiating Cells.
abstract: Glioblastoma-initiating cells (GIC) are a tumorigenic cell subpopulation resistant to radiotherapy and chemotherapy, and are a likely source of recurrence. However, the basis through which GICs are maintained has yet to be elucidated in detail. We herein demonstrated that the carcinoembryonic antigen-related cell adhesion molecule Ceacam1L acts as a crucial factor in GIC maintenance and tumorigenesis by activating c-Src/STAT3 signaling. Furthermore, we showed that monomers of the cytoplasmic domain of Ceacam1L bound to c-Src and STAT3 and induced their phosphorylation, whereas oligomerization of this domain ablated this function. Our results suggest that Ceacam1L-dependent adhesion between GIC and surrounding cells play an essential role in GIC maintenance and proliferation, as mediated by signals transmitted by monomeric forms of the Ceacam1L cytoplasmic domain.
authors.affiliation: Division of Stem Cell Biology, Institute for Genetic Medicine, Hokkaido University, Sapporo, Hokkaido, Japan. Department of Neurosurgery, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, Japan.
authors.forename: Sadahiro
authors.initials: S
authors.lastname: Kaneko
authors.affiliation: Laboratory for Cell Lineage Modulation, Center for Developmental Biology, RIKEN, Kobe, Hyogo, Japan.
authors.forename: Yuka
authors.initials: Y
authors.lastname: Nakatani
authors.affiliation: Laboratory for Cell Lineage Modulation, Center for Developmental Biology, RIKEN, Kobe, Hyogo, Japan. Department of Neurosurgery, Kumamoto University Graduate School of Medical Science, Kumamoto, Kumamoto, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Takezaki
authors.affiliation: Laboratory for Cell Lineage Modulation, Center for Developmental Biology, RIKEN, Kobe, Hyogo, Japan. Department of Neurosurgery, Kumamoto University Graduate School of Medical Science, Kumamoto, Kumamoto, Japan.
authors.forename: Takuichiro
authors.initials: T
authors.lastname: Hide
authors.affiliation: Department of Neurosurgery, Ehime University Graduate School of Medicine, To-on, Ehime, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Yamashita
authors.affiliation: Division of Stem Cell Biology, Institute for Genetic Medicine, Hokkaido University, Sapporo, Hokkaido, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Ohtsu
authors.affiliation: Department of Neurosurgery, Ehime University Graduate School of Medicine, To-on, Ehime, Japan.
authors.forename: Takanori
authors.initials: T
authors.lastname: Ohnishi
authors.affiliation: Department of Neurosurgery, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, Japan.
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Terasaka
authors.affiliation: Department of Neurosurgery, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, Japan.
authors.forename: Kiyohiro
authors.initials: K
authors.lastname: Houkin
authors.affiliation: Division of Stem Cell Biology, Institute for Genetic Medicine, Hokkaido University, Sapporo, Hokkaido, Japan. Laboratory for Cell Lineage Modulation, Center for Developmental Biology, RIKEN, Kobe, Hyogo, Japan. tkondo@igm.hokudai.ac.jp.
authors.forename: Toru
authors.initials: T
authors.lastname: Kondo
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000502:physiology*; D001254:Astrocytoma / Q000378:metabolism; D014408:Biomarkers, Tumor; D001932:Brain Neoplasms / Q000098:blood supply / Q000378:metabolism / Q000473:pathology; D000081247:CSK Tyrosine-Protein Kinase; D002272:Carcinoembryonic Antigen / Q000502:physiology*; D015815:Cell Adhesion Molecules / Q000502:physiology*; D002455:Cell Division; D000066673:Cell Self Renewal / Q000235:genetics; D020869:Gene Expression Profiling; D005909:Glioblastoma / Q000098:blood supply / Q000473:pathology*; D006801:Humans; D053208:Kaplan-Meier Estimate; D051379:Mice; D009363:Neoplasm Proteins / Q000502:physiology*; D014411:Neoplastic Stem Cells / Q000473:pathology*; D009389:Neovascularization, Pathologic / Q000503:physiopathology; D010766:Phosphorylation; D058105:Polymerization; D025941:Protein Interaction Mapping; D011499:Protein Processing, Post-Translational; D017434:Protein Structure, Tertiary; D050796:STAT3 Transcription Factor / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D055153:Stem Cell Niche; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured; D014410:Tumor Stem Cell Assay; D019061:src-Family Kinases / Q000502:physiology
chemical_list: D015703:Antigens, CD; D014408:Biomarkers, Tumor; C069847:CD66 antigens; D002272:Carcinoembryonic Antigen; C486183:Ceacam1 protein, mouse; D015815:Cell Adhesion Molecules; D009363:Neoplasm Proteins; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C494087:Stat3 protein, mouse; D000081247:CSK Tyrosine-Protein Kinase; D019061:src-Family Kinases; C000631346:CSK protein, human