title: Wnt/β-Catenin Signaling Activates Expression of the Bone-Related Transcription Factor RUNX2 in Select Human Osteosarcoma Cell Types.
abstract: Osteosarcoma is the most common malignant bone tumor in children and adolescents. Metastasis and poor responsiveness to chemotherapy in osteosarcoma correlates with over-expression of the runt-related transcription factor RUNX2, which normally plays a key role in osteogenic lineage commitment, osteoblast differentiation, and bone formation. Furthermore, WNT/β-catenin signaling is over-activated in osteosarcoma and promotes tumor progression. Importantly, the WNT/β-catenin pathway normally activates RUNX2 gene expression during osteogenic lineage commitment. Therefore, we examined whether the WNT/β-catenin pathway controls the tumor-related elevation of RUNX2 expression in osteosarcoma. We analyzed protein levels and nuclear localization of β-catenin and RUNX2 in a panel of human osteosarcoma cell lines (SAOS, MG63, U2OS, HOS, G292, and 143B). In all six cell lines, β-catenin and RUNX2 are expressed to different degrees and localized in the nucleus and/or cytoplasm. SAOS cells have the highest levels of RUNX2 protein that is localized in the nucleus, while MG63 cells have the lowest RUNX2 levels which is mostly localized in the cytoplasm. Levels of β-catenin and RUNX2 protein are enhanced in HOS, G292, and 143B cells after treatment with the GSK3β inhibitor SB216763. Furthermore, small interfering RNA (siRNA)-mediated depletion of β-catenin inhibits RUNX2 expression in G292 cells. Thus, WNT/β-catenin activation is required for RUNX2 expression in at least some osteosarcoma cell types, where RUNX2 is known to promote expression of metastasis related genes. J. Cell. Biochem. 118: 3662-3674, 2017. © 2017 Wiley Periodicals, Inc.
authors.affiliation: Program of Cellular and Molecular Biology, Institute of Biomedical Sciences (ICBM), Faculty of Medicine, University of Chile, Santiago, 8380453, Chile.|Millennium Institute on Immunology and Immunotherapy, Faculty of Medicine, University of Chile, Santiago 8380453, Chile.
authors.forename: Oscar A
authors.initials: OA
authors.lastname: Vega
authors.affiliation: Program of Cellular and Molecular Biology, Institute of Biomedical Sciences (ICBM), Faculty of Medicine, University of Chile, Santiago, 8380453, Chile.|Millennium Institute on Immunology and Immunotherapy, Faculty of Medicine, University of Chile, Santiago 8380453, Chile.
authors.forename: Claudia M J
authors.initials: CMJ
authors.lastname: Lucero
authors.affiliation: Program of Cellular and Molecular Biology, Institute of Biomedical Sciences (ICBM), Faculty of Medicine, University of Chile, Santiago, 8380453, Chile.|Millennium Institute on Immunology and Immunotherapy, Faculty of Medicine, University of Chile, Santiago 8380453, Chile.
authors.forename: Hector F
authors.initials: HF
authors.lastname: Araya
authors.affiliation: Program of Cellular and Molecular Biology, Institute of Biomedical Sciences (ICBM), Faculty of Medicine, University of Chile, Santiago, 8380453, Chile.|Millennium Institute on Immunology and Immunotherapy, Faculty of Medicine, University of Chile, Santiago 8380453, Chile.
authors.forename: Sofia
authors.initials: S
authors.lastname: Jerez
authors.affiliation: Program of Cellular and Molecular Biology, Institute of Biomedical Sciences (ICBM), Faculty of Medicine, University of Chile, Santiago, 8380453, Chile.
authors.forename: Julio C
authors.initials: JC
authors.lastname: Tapia
authors.affiliation: Program of Cellular and Molecular Biology, Institute of Biomedical Sciences (ICBM), Faculty of Medicine, University of Chile, Santiago, 8380453, Chile.
authors.forename: Marcelo
authors.initials: M
authors.lastname: Antonelli
authors.affiliation: Millennium Institute on Immunology and Immunotherapy, Faculty of Medicine, University of Chile, Santiago 8380453, Chile.|Program of Immunology, Institute of Biomedical Sciences (ICBM), Faculty of Medicine, University of Chile, Santiago 8380453, Chile.
authors.forename: Flavio
authors.initials: F
authors.lastname: Salazar-Onfray
authors.affiliation: Department of Anatomical Pathology, University of Chile Clinical Hospital, Santiago 8380456, Chile.|Department of Pathology, Clinica Las Condes, Santiago 7591018, Chile.
authors.forename: Facundo
authors.initials: F
authors.lastname: Las Heras
authors.affiliation: Departments of Orthopedic Surgery and Biochemistry and Molecular Biology, Mayo Clinic, Rochester 55905, Minnesota.
authors.forename: Roman
authors.initials: R
authors.lastname: Thaler
authors.affiliation: Departments of Orthopedic Surgery and Biochemistry and Molecular Biology, Mayo Clinic, Rochester 55905, Minnesota.
authors.forename: Scott M
authors.initials: SM
authors.lastname: Riester
authors.affiliation: Department of Biochemistry and University of Vermont Cancer Center, The Robert Larner College of Medicine, University of Vermont, Burlington 05405, Vermont.
authors.forename: Gary S
authors.initials: GS
authors.lastname: Stein
authors.affiliation: Departments of Orthopedic Surgery and Biochemistry and Molecular Biology, Mayo Clinic, Rochester 55905, Minnesota.
authors.forename: Andre J
authors.initials: AJ
authors.lastname: van Wijnen
authors.affiliation: Program of Cellular and Molecular Biology, Institute of Biomedical Sciences (ICBM), Faculty of Medicine, University of Chile, Santiago, 8380453, Chile.|Millennium Institute on Immunology and Immunotherapy, Faculty of Medicine, University of Chile, Santiago 8380453, Chile.
authors.forename: Mario A
authors.identifier: 0000-0001-6184-0829
authors.initials: MA
authors.lastname: Galindo
mesh_terms: D001859:Bone Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D050659:Core Binding Factor Alpha 1 Subunit / Q000096:biosynthesis* / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D012516:Osteosarcoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D060449:Wnt Signaling Pathway
chemical_list: D050659:Core Binding Factor Alpha 1 Subunit; D009363:Neoplasm Proteins; C493709:RUNX2 protein, human
keywords: CANCER; ONCOGENE; OSTEOSARCOMA; RUNX2 TRANSCRIPTION FACTOR; Wnt/β-CATENIN