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Keywords {🔍}

tlx, cells, cell, mmp, article, neural, google, scholar, figure, cas, imr, tumor, stem, spheres, expression, cancer, control, promoter, oct, lines, migration, nature, nuclear, binding, invasion, usa, analysis, neuroblastoma, media, hypoxia, levels, performed, role, formation, primary, selfrenewal, migratory, matrix, tissues, tlxsilenced, data, receptor, gene, compared, results, expressed, sknbec, factor, assay, staining,

Topics {✒️}

nature publishing group open-access journal published nature portfolio privacy policy obese diabetic/severe-combined immunodeficiency invasion/migration index values advertising synthesized ethyl 2-[n-p-chlorobenzyl nature 2006 nature 2004 nature wnt/beta-catenin signalling east rutherford author information authors china z biology open 2012 nl/cgi-bin/r2/main 0 reprints orphan nuclear receptor middle india stabilized beta-catenin functions neural stem/progenitor cell atp binding cassette-g2 mouse/rabbit igg served notch/rbp-jkappa complex epstein–barr virus contamination biotin-labeled consensus oligos author correspondence mycn-amplified cell lines mycn-amplified cell lines castration-resistant prostate cancer product–moment correlation coefficient cell-cycle programs contributing von hippel–lindau protein tlx-expressing tic clusters hrp-conjugated anti-mouse harbor tumor-initiating cells enhances β-catenin activation sharing neuroblastoma data gene expression signature sphere-forming cells showed paraffin-embedded tissue sections cell line-specific effect tlx-expressing tumor clusters nb tumor-initiating cells seeding single-cell suspension putative tlx-binding sites nuclear receptor tlx tlx-depleted cells decreased

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         headline:TLX activates MMP-2, promotes self-renewal of tumor spheres in neuroblastoma and correlates with poor patient survival
         description:Nuclear orphan receptor TLX (Drosophila tailless homolog) is essential for the maintenance of neural stem/progenitor cell self-renewal, but its role in neuroblastoma (NB) is not well understood. Here, we show that TLX is essential for the formation of tumor spheres in three different NB cell lines, when grown in neural stem cell media. We demonstrate that the knock down of TLX in IMR-32 cells diminishes its tumor sphere-forming capacity. In tumor spheres, TLX is coexpressed with the neural progenitor markers Nestin, CD133 and Oct-4. In addition, TLX is coexpressed with the migratory neural progenitor markers CD15 and matrix metalloproteinase-2 (MMP-2) in xenografts of primary NB cells from patients. Subsequently, we show the effect of TLX on the proliferative, invasive and migratory properties of IMR-32 cells. We attribute this to the recruitment of TLX to both MMP-2 and Oct-4 gene promoters, which resulted in the respective gene activation. In support of our findings, we found that TLX expression was high in NB patient tissues when compared with normal peripheral nervous system tissues. Further, the Kaplan–Meier estimator indicated a negative correlation between TLX expression and survival in 88 NB patients. Therefore, our results point at TLX being a crucial player in progression of NB, by promoting self-renewal of NB tumor-initiating cells and altering their migratory and invasive properties.
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      headline:TLX activates MMP-2, promotes self-renewal of tumor spheres in neuroblastoma and correlates with poor patient survival
      description:Nuclear orphan receptor TLX (Drosophila tailless homolog) is essential for the maintenance of neural stem/progenitor cell self-renewal, but its role in neuroblastoma (NB) is not well understood. Here, we show that TLX is essential for the formation of tumor spheres in three different NB cell lines, when grown in neural stem cell media. We demonstrate that the knock down of TLX in IMR-32 cells diminishes its tumor sphere-forming capacity. In tumor spheres, TLX is coexpressed with the neural progenitor markers Nestin, CD133 and Oct-4. In addition, TLX is coexpressed with the migratory neural progenitor markers CD15 and matrix metalloproteinase-2 (MMP-2) in xenografts of primary NB cells from patients. Subsequently, we show the effect of TLX on the proliferative, invasive and migratory properties of IMR-32 cells. We attribute this to the recruitment of TLX to both MMP-2 and Oct-4 gene promoters, which resulted in the respective gene activation. In support of our findings, we found that TLX expression was high in NB patient tissues when compared with normal peripheral nervous system tissues. Further, the Kaplan–Meier estimator indicated a negative correlation between TLX expression and survival in 88 NB patients. Therefore, our results point at TLX being a crucial player in progression of NB, by promoting self-renewal of NB tumor-initiating cells and altering their migratory and invasive properties.
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      name:P L Chavali
      affiliation:
            name:Sahlgrenska Cancer Center at the Sahlgrenska Academy, University of Gothenburg, Box 425
            address:
               name:Sahlgrenska Cancer Center at the Sahlgrenska Academy, University of Gothenburg, Box 425, Gothenburg SE 40530, Sweden
               type:PostalAddress
            type:Organization
            name:University of Cambridge, Li Ka Shing Centre, Robinson Way
            address:
               name:Department of Oncology, University of Cambridge, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK
               type:PostalAddress
            type:Organization
      name:R K R Saini
      affiliation:
            name:Sahlgrenska Cancer Center at the Sahlgrenska Academy, University of Gothenburg, Box 425
            address:
               name:Sahlgrenska Cancer Center at the Sahlgrenska Academy, University of Gothenburg, Box 425, Gothenburg SE 40530, Sweden
               type:PostalAddress
            type:Organization
      name:Q Zhai
      affiliation:
            name:Sahlgrenska Cancer Center at the Sahlgrenska Academy, University of Gothenburg, Box 425
            address:
               name:Sahlgrenska Cancer Center at the Sahlgrenska Academy, University of Gothenburg, Box 425, Gothenburg SE 40530, Sweden
               type:PostalAddress
            type:Organization
      name:D Vizlin-Hodzic
      affiliation:
            name:Sahlgrenska Cancer Center at the Sahlgrenska Academy, University of Gothenburg, Box 425
            address:
               name:Sahlgrenska Cancer Center at the Sahlgrenska Academy, University of Gothenburg, Box 425, Gothenburg SE 40530, Sweden
               type:PostalAddress
            type:Organization
      name:S Venkatabalasubramanian
      affiliation:
            name:Sahlgrenska Cancer Center at the Sahlgrenska Academy, University of Gothenburg, Box 425
            address:
               name:Sahlgrenska Cancer Center at the Sahlgrenska Academy, University of Gothenburg, Box 425, Gothenburg SE 40530, Sweden
               type:PostalAddress
            type:Organization
            name:School of Chemical and Biotechnology, SASTRA University
            address:
               name:School of Chemical and Biotechnology, SASTRA University, Thanjavur 613401, India
               type:PostalAddress
            type:Organization
      name:A Hayashi
      affiliation:
            name:Sahlgrenska Cancer Center at the Sahlgrenska Academy, University of Gothenburg, Box 425
            address:
               name:Sahlgrenska Cancer Center at the Sahlgrenska Academy, University of Gothenburg, Box 425, Gothenburg SE 40530, Sweden
               type:PostalAddress
            type:Organization
      name:E Johansson
      affiliation:
            name:Sahlgrenska Cancer Center at the Sahlgrenska Academy, University of Gothenburg, Box 425
            address:
               name:Sahlgrenska Cancer Center at the Sahlgrenska Academy, University of Gothenburg, Box 425, Gothenburg SE 40530, Sweden
               type:PostalAddress
            type:Organization
      name:Z-j Zeng
      affiliation:
            name:Sahlgrenska Cancer Center at the Sahlgrenska Academy, University of Gothenburg, Box 425
            address:
               name:Sahlgrenska Cancer Center at the Sahlgrenska Academy, University of Gothenburg, Box 425, Gothenburg SE 40530, Sweden
               type:PostalAddress
            type:Organization
            name:Molecular Biology Research Center, School of Biological Science and Technology, Central South University
            address:
               name:Molecular Biology Research Center, School of Biological Science and Technology, Central South University, Changsha, China
               type:PostalAddress
            type:Organization
      name:S Mohlin
      affiliation:
            name:Center for Molecular Pathology, Lund University, SkÃ¥ne University Hospital
            address:
               name:Center for Molecular Pathology, Lund University, SkÃ¥ne University Hospital, Malmö SE 20502, Sweden
               type:PostalAddress
            type:Organization
      name:S PÃ¥hlman
      affiliation:
            name:Center for Molecular Pathology, Lund University, SkÃ¥ne University Hospital
            address:
               name:Center for Molecular Pathology, Lund University, SkÃ¥ne University Hospital, Malmö SE 20502, Sweden
               type:PostalAddress
            type:Organization
      name:L Hansford
      affiliation:
            name:Program in Cell Biology, Hospital for Sick Children
            address:
               name:Program in Cell Biology, Hospital for Sick Children, Toronto, Canada
               type:PostalAddress
            type:Organization
            name:University of Toronto
            address:
               name:Department of Molecular Genetics, University of Toronto, Toronto, Canada
               type:PostalAddress
            type:Organization
      name:D R Kaplan
      affiliation:
            name:Program in Cell Biology, Hospital for Sick Children
            address:
               name:Program in Cell Biology, Hospital for Sick Children, Toronto, Canada
               type:PostalAddress
            type:Organization
            name:University of Toronto
            address:
               name:Department of Molecular Genetics, University of Toronto, Toronto, Canada
               type:PostalAddress
            type:Organization
      name:K Funa
      affiliation:
            name:Sahlgrenska Cancer Center at the Sahlgrenska Academy, University of Gothenburg, Box 425
            address:
               name:Sahlgrenska Cancer Center at the Sahlgrenska Academy, University of Gothenburg, Box 425, Gothenburg SE 40530, Sweden
               type:PostalAddress
            type:Organization
      email:[email protected]
PostalAddress:
      name:Sahlgrenska Cancer Center at the Sahlgrenska Academy, University of Gothenburg, Box 425, Gothenburg SE 40530, Sweden
      name:Department of Oncology, University of Cambridge, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK
      name:Sahlgrenska Cancer Center at the Sahlgrenska Academy, University of Gothenburg, Box 425, Gothenburg SE 40530, Sweden
      name:Sahlgrenska Cancer Center at the Sahlgrenska Academy, University of Gothenburg, Box 425, Gothenburg SE 40530, Sweden
      name:Sahlgrenska Cancer Center at the Sahlgrenska Academy, University of Gothenburg, Box 425, Gothenburg SE 40530, Sweden
      name:Sahlgrenska Cancer Center at the Sahlgrenska Academy, University of Gothenburg, Box 425, Gothenburg SE 40530, Sweden
      name:School of Chemical and Biotechnology, SASTRA University, Thanjavur 613401, India
      name:Sahlgrenska Cancer Center at the Sahlgrenska Academy, University of Gothenburg, Box 425, Gothenburg SE 40530, Sweden
      name:Sahlgrenska Cancer Center at the Sahlgrenska Academy, University of Gothenburg, Box 425, Gothenburg SE 40530, Sweden
      name:Sahlgrenska Cancer Center at the Sahlgrenska Academy, University of Gothenburg, Box 425, Gothenburg SE 40530, Sweden
      name:Molecular Biology Research Center, School of Biological Science and Technology, Central South University, Changsha, China
      name:Center for Molecular Pathology, Lund University, SkÃ¥ne University Hospital, Malmö SE 20502, Sweden
      name:Center for Molecular Pathology, Lund University, SkÃ¥ne University Hospital, Malmö SE 20502, Sweden
      name:Program in Cell Biology, Hospital for Sick Children, Toronto, Canada
      name:Department of Molecular Genetics, University of Toronto, Toronto, Canada
      name:Program in Cell Biology, Hospital for Sick Children, Toronto, Canada
      name:Department of Molecular Genetics, University of Toronto, Toronto, Canada
      name:Sahlgrenska Cancer Center at the Sahlgrenska Academy, University of Gothenburg, Box 425, Gothenburg SE 40530, Sweden

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