title: The NSL Chromatin-Modifying Complex Subunit KANSL2 Regulates Cancer Stem-like Properties in Glioblastoma That Contribute to Tumorigenesis.
abstract: KANSL2 is an integral subunit of the nonspecific lethal (NSL) chromatin-modifying complex that contributes to epigenetic programs in embryonic stem cells. In this study, we report a role for KANSL2 in regulation of stemness in glioblastoma (GBM), which is characterized by heterogeneous tumor stem-like cells associated with therapy resistance and disease relapse. KANSL2 expression is upregulated in cancer cells, mainly at perivascular regions of tumors. RNAi-mediated silencing of KANSL2 in GBM cells impairs their tumorigenic capacity in mouse xenograft models. In clinical specimens, we found that expression levels of KANSL2 correlate with stemness markers in GBM stem-like cell populations. Mechanistic investigations showed that KANSL2 regulates cell self-renewal, which correlates with effects on expression of the stemness transcription factor POU5F1. RNAi-mediated silencing of POU5F1 reduced KANSL2 levels, linking these two genes to stemness control in GBM cells. Together, our findings indicate that KANSL2 acts to regulate the stem cell population in GBM, defining it as a candidate GBM biomarker for clinical use. Cancer Res; 76(18); 5383-94. ©2016 AACR.
authors.affiliation: Instituto de Investigación en Biomedicina de Buenos Aires (IBioBA)-CONICET -Partner Institute of the Max Planck Society, Buenos Aires, Argentina.
authors.forename: Nazarena E
authors.initials: NE
authors.lastname: Ferreyra Solari
authors.affiliation: Instituto de Investigación en Biomedicina de Buenos Aires (IBioBA)-CONICET -Partner Institute of the Max Planck Society, Buenos Aires, Argentina.
authors.forename: Fiorella S
authors.initials: FS
authors.lastname: Belforte
authors.affiliation: Instituto de Investigación en Biomedicina de Buenos Aires (IBioBA)-CONICET -Partner Institute of the Max Planck Society, Buenos Aires, Argentina.
authors.forename: Lucía
authors.initials: L
authors.lastname: Canedo
authors.affiliation: Laboratorio de Investigación aplicada a Neurociencias (LIAN), Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia (FLENI), Buenos Aires, Argentina.
authors.forename: Guillermo A
authors.initials: GA
authors.lastname: Videla-Richardson
authors.affiliation: Linda Crnic Institute for Down Syndrome, Department of Pharmacology, University of Colorado School of Medicine, Aurora, Colorado.
authors.forename: Joaquín M
authors.initials: JM
authors.lastname: Espinosa
authors.affiliation: Instituto de Investigación en Biomedicina de Buenos Aires (IBioBA)-CONICET -Partner Institute of the Max Planck Society, Buenos Aires, Argentina.
authors.forename: Mario
authors.initials: M
authors.lastname: Rossi
authors.affiliation: Servicio Análisis Multigénico, Unidad Central de Investigación, Facultad de Medicina, Universidad de Valencia, Valencia, España.
authors.forename: Eva
authors.initials: E
authors.lastname: Serna
authors.affiliation: Laboratorio de Biología Molecular, Departamento de Neuropatología y Biología Molecular, Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia (FLENI), Buenos Aires, Argentina. Laboratorio de Histopatología, Cuerpo Médico Forense, Tribunal Supremo de Justicia, Buenos Aires, Argentina.
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Riudavets
authors.affiliation: Laboratorio de Biología Molecular, Departamento de Neuropatología y Biología Molecular, Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia (FLENI), Buenos Aires, Argentina.
authors.forename: Horacio
authors.initials: H
authors.lastname: Martinetto
authors.affiliation: Laboratorio de Biología Molecular, Departamento de Neuropatología y Biología Molecular, Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia (FLENI), Buenos Aires, Argentina.
authors.forename: Gustavo
authors.initials: G
authors.lastname: Sevlever
authors.affiliation: Instituto de Investigación en Biomedicina de Buenos Aires (IBioBA)-CONICET -Partner Institute of the Max Planck Society, Buenos Aires, Argentina. cperezcastro@ibioba-mpsp-conicet.gov.ar.
authors.forename: Carolina
authors.initials: C
authors.lastname: Perez-Castro
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D014408:Biomarkers, Tumor / Q000032:analysis; D015153:Blotting, Western; D001932:Brain Neoplasms / Q000473:pathology*; D063646:Carcinogenesis / Q000378:metabolism*; D002469:Cell Separation; D005260:Female; D005434:Flow Cytometry; D055785:Gene Knockdown Techniques; D005909:Glioblastoma / Q000473:pathology*; D064593:Heterografts; D051548:Histone Acetyltransferases / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008875:Middle Aged; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology; D009687:Nuclear Proteins; D020411:Oligonucleotide Array Sequence Analysis; D060888:Real-Time Polymerase Chain Reaction; D015854:Up-Regulation
chemical_list: D014408:Biomarkers, Tumor; D009687:Nuclear Proteins; D051548:Histone Acetyltransferases; C496552:KAT8 protein, human