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Title:
TLX activates MMP-2, promotes self-renewal of tumor spheres in neuroblastoma and correlates with poor patient survival | Cell Death & Disease
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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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,
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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 KaplanâMeier 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 KaplanâMeier 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: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, Skåne University Hospital
address:
name:Center for Molecular Pathology, Lund University, Skåne University Hospital, Malmö SE 20502, Sweden
type:PostalAddress
type:Organization
name:S PÃ¥hlman
affiliation:
name:Center for Molecular Pathology, Lund University, Skåne University Hospital
address:
name:Center for Molecular Pathology, Lund University, Skåne 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, Skåne University Hospital, Malmö SE 20502, Sweden
name:Center for Molecular Pathology, Lund University, Skåne 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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