Identification of non-canonical NF-κB signaling as a critical mediator of Smac mimetic-stimulated migration and invasion of glioblastoma cells View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2013-03

AUTHORS

A Tchoghandjian, C Jennewein, I Eckhardt, K Rajalingam, S Fulda

ABSTRACT

As inhibitor of apoptosis (IAP) proteins can regulate additional signaling pathways beyond apoptosis, we investigated the effect of the second mitochondrial activator of caspases (Smac) mimetic BV6, which antagonizes IAP proteins, on non-apoptotic functions in glioblastoma (GBM). Here, we identify non-canonical nuclear factor-κB (NF-κB) signaling and a tumor necrosis factor-α (TNFα)/TNF receptor 1 (TNFR1) autocrine/paracrine loop as critical mediators of BV6-stimulated migration and invasion of GBM cells. In addition to GBM cell lines, BV6 triggers cell elongation, migration and invasion in primary, patient-derived GBM cells at non-toxic concentrations, which do not affect cell viability or proliferation, and also increases infiltrative tumor growth in vivo underscoring the relevance of these findings. Molecular studies reveal that BV6 causes rapid degradation of cellular IAP proteins, accumulation of NIK, processing of p100 to p52, translocation of p52 into the nucleus, increased NF-κB DNA binding and enhanced NF-κB transcriptional activity. Electrophoretic mobility shift assay supershift shows that the NF-κB DNA-binding subunits consist of p50, p52 and RelB further confirming the activation of the non-canonical NF-κB pathway. BV6-stimulated NF-κB activation leads to elevated mRNA levels of TNFα and additional NF-κB target genes involved in migration (i.e., interleukin 8, monocyte chemoattractant protein 1, CXC chemokine receptor 4) and invasion (i.e., matrix metalloproteinase-9). Importantly, inhibition of NF-κB by overexpression of dominant-negative IκBα superrepressor prevents the BV6-stimulated cell elongation, migration and invasion. Similarly, specific inhibition of non-canonical NF-κB signaling by RNA interference-mediated silencing of NIK suppresses the BV6-induced cell elongation, migration and invasion as well as upregulation of NF-κB target genes. Intriguingly, pharmacological or genetic inhibition of the BV6-stimulated TNFα autocrine/paracrine loop by the TNFα-blocking antibody Enbrel or by knockdown of TNFR1 abrogates BV6-induced cell elongation, migration and invasion. By demonstrating that the Smac mimetic BV6 at non-toxic concentrations promotes migration and invasion of GBM cells via non-canonical NF-κB signaling, our findings have important implications for the use of Smac mimetics as cancer therapeutics. More... »

PAGES

e564

References to SciGraph publications

  • 2008-12. Nonredundant and complementary functions of TRAF2 and TRAF3 in a ubiquitination cascade that activates NIK-dependent alternative NF-κB signaling in NATURE IMMUNOLOGY
  • 2011-08. Crosstalk in NF-κB signaling pathways in NATURE IMMUNOLOGY
  • 2005-10. Betulinic acid as new activator of NF-κB: molecular mechanisms and implications for cancer therapy in ONCOGENE
  • 2009-09. Histone deacetylase inhibitors cooperate with IFN-γ to restore caspase-8 expression and overcome TRAIL resistance in cancers with silencing of caspase-8 in ONCOGENE
  • 2006-05. Nuclear factor inducing kinase: A key regulator in osteopontin- induced MAPK/IκB kinase dependent NF-κB-mediated promatrix metalloproteinase-9 activation in GLYCOCONJUGATE JOURNAL
  • 2001-11. Transcription of the RelB gene is regulated by NF-κB in ONCOGENE
  • 2013-02. Smac mimetic sensitizes glioblastoma cells to Temozolomide-induced apoptosis in a RIP1- and NF-κB-dependent manner in ONCOGENE
  • 2010-02. TNF-α/NF-κB/Snail pathway in cancer cell migration and invasion in BRITISH JOURNAL OF CANCER
  • 2008-12. Noncanonical NF-κB activation requires coordinated assembly of a regulatory complex of the adaptors cIAP1, cIAP2, TRAF2 and TRAF3 and the kinase NIK in NATURE IMMUNOLOGY
  • 2012-02. Targeting IAP proteins for therapeutic intervention in cancer in NATURE REVIEWS DRUG DISCOVERY
  • 2007-10-02. Diffuse glioma growth: a guerilla war in ACTA NEUROPATHOLOGICA
  • 1999-04. Expression and biological activity of X-linked inhibitor of apoptosis (XIAP) in human malignant glioma in CELL DEATH & DIFFERENTIATION
  • 2008-12. X-linked and cellular IAPs modulate the stability of C-RAF kinase and cell motility in NATURE CELL BIOLOGY
  • 2005-12. Expression of the constitutively activated RelA/NF-κB in human astrocytic tumors and the in vitro implication in the regulation of urokinase-type plasminogen activator, migration, and invasion in BRAIN TUMOR PATHOLOGY
  • 2007-10. Aberrant constitutive activation of nuclear factor κB in glioblastoma multiforme drives invasive phenotype in JOURNAL OF NEURO-ONCOLOGY
  • 2007-01. Regulation of TRAIL-induced apoptosis by XIAP in pancreatic carcinoma cells in ONCOGENE
  • 2012-08. Impairment of lysosomal integrity by B10, a glycosylated derivative of betulinic acid, leads to lysosomal cell death and converts autophagy into a detrimental process in CELL DEATH & DIFFERENTIATION
  • 2002-08. Smac agonists sensitize for Apo2L/TRAIL- or anticancer drug-induced apoptosis and induce regression of malignant glioma in vivo in NATURE MEDICINE
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/cddis.2013.70

    DOI

    http://dx.doi.org/10.1038/cddis.2013.70

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1007250168

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/23538445


    Indexing Status Check whether this publication has been indexed by Scopus and Web Of Science using the SN Indexing Status Tool
    Incoming Citations Browse incoming citations for this publication using opencitations.net

    JSON-LD is the canonical representation for SciGraph data.

    TIP: You can open this SciGraph record using an external JSON-LD service: JSON-LD Playground Google SDTT

    [
      {
        "@context": "https://springernature.github.io/scigraph/jsonld/sgcontext.json", 
        "about": [
          {
            "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/0601", 
            "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
            "name": "Biochemistry and Cell Biology", 
            "type": "DefinedTerm"
          }, 
          {
            "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/06", 
            "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
            "name": "Biological Sciences", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Brain Neoplasms", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Cell Line, Tumor", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Cell Movement", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Etanercept", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Gene Expression Regulation, Neoplastic", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Glioblastoma", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Humans", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Immunoglobulin G", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Inhibitor of Apoptosis Proteins", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Intracellular Signaling Peptides and Proteins", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Mitochondrial Proteins", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "NF-kappa B", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Neoplasm Invasiveness", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Peptidomimetics", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Protein Subunits", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "RNA, Small Interfering", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Receptors, Tumor Necrosis Factor", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Receptors, Tumor Necrosis Factor, Type I", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Signal Transduction", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Tumor Necrosis Factor-alpha", 
            "type": "DefinedTerm"
          }
        ], 
        "author": [
          {
            "affiliation": {
              "alternateName": "Goethe University Frankfurt", 
              "id": "https://www.grid.ac/institutes/grid.7839.5", 
              "name": [
                "Institute for Experimental Cancer Research in Pediatrics, Goethe University, Frankfurt, Germany"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Tchoghandjian", 
            "givenName": "A", 
            "id": "sg:person.01203762303.45", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01203762303.45"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Goethe University Frankfurt", 
              "id": "https://www.grid.ac/institutes/grid.7839.5", 
              "name": [
                "Institute for Experimental Cancer Research in Pediatrics, Goethe University, Frankfurt, Germany"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Jennewein", 
            "givenName": "C", 
            "id": "sg:person.01220446253.14", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01220446253.14"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Goethe University Frankfurt", 
              "id": "https://www.grid.ac/institutes/grid.7839.5", 
              "name": [
                "Institute for Experimental Cancer Research in Pediatrics, Goethe University, Frankfurt, Germany"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Eckhardt", 
            "givenName": "I", 
            "id": "sg:person.01017251224.26", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01017251224.26"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Goethe University Frankfurt", 
              "id": "https://www.grid.ac/institutes/grid.7839.5", 
              "name": [
                "Emmy Noether Group of the DFG, Institute of Biochemistry II, Goethe University Medical School, Frankfurt, Germany"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Rajalingam", 
            "givenName": "K", 
            "id": "sg:person.01152534517.15", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01152534517.15"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Goethe University Frankfurt", 
              "id": "https://www.grid.ac/institutes/grid.7839.5", 
              "name": [
                "Institute for Experimental Cancer Research in Pediatrics, Goethe University, Frankfurt, Germany"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Fulda", 
            "givenName": "S", 
            "id": "sg:person.01331656400.85", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01331656400.85"
            ], 
            "type": "Person"
          }
        ], 
        "citation": [
          {
            "id": "https://doi.org/10.1073/pnas.95.7.3792", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1000474592"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/sj.onc.1209776", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1001145043", 
              "https://doi.org/10.1038/sj.onc.1209776"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/sj.onc.1209776", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1001145043", 
              "https://doi.org/10.1038/sj.onc.1209776"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1593/neo.09436", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1006077979"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1038/sj.embor.7400795", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1006661587"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/ni.2065", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1006965315", 
              "https://doi.org/10.1038/ni.2065"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/j.ccr.2009.11.021", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1008831547"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1074/jbc.m110.216226", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1009588501"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1111/j.1582-4934.2009.00888.x", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1015845763"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1111/j.1582-4934.2009.00888.x", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1015845763"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/cdd.2012.10", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1016341290", 
              "https://doi.org/10.1038/cdd.2012.10"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/ni.1678", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1017708694", 
              "https://doi.org/10.1038/ni.1678"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/sj.bjc.6605530", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1017883550", 
              "https://doi.org/10.1038/sj.bjc.6605530"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/sj.bjc.6605530", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1017883550", 
              "https://doi.org/10.1038/sj.bjc.6605530"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/ncb1804", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1017925206", 
              "https://doi.org/10.1038/ncb1804"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1007/s00401-007-0293-7", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1019580592", 
              "https://doi.org/10.1007/s00401-007-0293-7"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1007/s00401-007-0293-7", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1019580592", 
              "https://doi.org/10.1007/s00401-007-0293-7"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1152/ajpheart.00180.2010", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1019966031"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nm735", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1020239862", 
              "https://doi.org/10.1038/nm735"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nm735", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1020239862", 
              "https://doi.org/10.1038/nm735"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/s0092-8674(00)00009-x", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1021931408"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1002/ijc.22729", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1024107340"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1074/jbc.c800128200", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1024459927"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1128/mcb.14.12.7695", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1024709479"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nrd3627", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1025792112", 
              "https://doi.org/10.1038/nrd3627"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.4049/jimmunol.0903131", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1025846006"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1002/hep.22393", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1026491192"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/j.molcel.2008.05.014", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1027166093"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/onc.2009.161", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1028121111", 
              "https://doi.org/10.1038/onc.2009.161"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1038/emboj.2011.423", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1030004367"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/j.cell.2007.10.037", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1032826025"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.4049/jimmunol.1102454", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1033171277"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/s0092-8674(00)00008-8", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1033773534"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1158/0008-5472.can-07-5173", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1034206312"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/j.cell.2007.10.030", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1036164945"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/sj.onc.1208842", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1036583697", 
              "https://doi.org/10.1038/sj.onc.1208842"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/sj.onc.1208842", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1036583697", 
              "https://doi.org/10.1038/sj.onc.1208842"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/sj.onc.1208842", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1036583697", 
              "https://doi.org/10.1038/sj.onc.1208842"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/j.molcel.2011.04.008", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1037526336"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1007/s10719-006-7927-1", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1040188397", 
              "https://doi.org/10.1007/s10719-006-7927-1"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/sj.cdd.4400503", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1042692074", 
              "https://doi.org/10.1038/sj.cdd.4400503"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/sj.cdd.4400503", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1042692074", 
              "https://doi.org/10.1038/sj.cdd.4400503"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1158/1078-0432.ccr-11-0075", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1043146275"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1242/jcs.075770", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1043720963"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1007/s10014-005-0186-1", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1045630891", 
              "https://doi.org/10.1007/s10014-005-0186-1"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1007/s10014-005-0186-1", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1045630891", 
              "https://doi.org/10.1007/s10014-005-0186-1"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/sj.onc.1204868", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1045634373", 
              "https://doi.org/10.1038/sj.onc.1204868"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/sj.onc.1204868", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1045634373", 
              "https://doi.org/10.1038/sj.onc.1204868"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1007/s11060-007-9390-7", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1046986451", 
              "https://doi.org/10.1007/s11060-007-9390-7"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/onc.2012.108", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1050959459", 
              "https://doi.org/10.1038/onc.2012.108"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1074/jbc.m110.176982", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1051563020"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1158/1535-7163.mct-11-0218", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1053405385"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/ni.1676", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1053487240", 
              "https://doi.org/10.1038/ni.1676"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1126/science.278.5339.866", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1062558523"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1200/jco.20.4.1063", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1064202816"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1200/jco.2003.05.063", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1064203593"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://app.dimensions.ai/details/publication/pub.1082862824", 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://app.dimensions.ai/details/publication/pub.1083167141", 
            "type": "CreativeWork"
          }
        ], 
        "datePublished": "2013-03", 
        "datePublishedReg": "2013-03-01", 
        "description": "As inhibitor of apoptosis (IAP) proteins can regulate additional signaling pathways beyond apoptosis, we investigated the effect of the second mitochondrial activator of caspases (Smac) mimetic BV6, which antagonizes IAP proteins, on non-apoptotic functions in glioblastoma (GBM). Here, we identify non-canonical nuclear factor-\u03baB (NF-\u03baB) signaling and a tumor necrosis factor-\u03b1 (TNF\u03b1)/TNF receptor 1 (TNFR1) autocrine/paracrine loop as critical mediators of BV6-stimulated migration and invasion of GBM cells. In addition to GBM cell lines, BV6 triggers cell elongation, migration and invasion in primary, patient-derived GBM cells at non-toxic concentrations, which do not affect cell viability or proliferation, and also increases infiltrative tumor growth in vivo underscoring the relevance of these findings. Molecular studies reveal that BV6 causes rapid degradation of cellular IAP proteins, accumulation of NIK, processing of p100 to p52, translocation of p52 into the nucleus, increased NF-\u03baB DNA binding and enhanced NF-\u03baB transcriptional activity. Electrophoretic mobility shift assay supershift shows that the NF-\u03baB DNA-binding subunits consist of p50, p52 and RelB further confirming the activation of the non-canonical NF-\u03baB pathway. BV6-stimulated NF-\u03baB activation leads to elevated mRNA levels of TNF\u03b1 and additional NF-\u03baB target genes involved in migration (i.e., interleukin 8, monocyte chemoattractant protein 1, CXC chemokine receptor 4) and invasion (i.e., matrix metalloproteinase-9). Importantly, inhibition of NF-\u03baB by overexpression of dominant-negative I\u03baB\u03b1 superrepressor prevents the BV6-stimulated cell elongation, migration and invasion. Similarly, specific inhibition of non-canonical NF-\u03baB signaling by RNA interference-mediated silencing of NIK suppresses the BV6-induced cell elongation, migration and invasion as well as upregulation of NF-\u03baB target genes. Intriguingly, pharmacological or genetic inhibition of the BV6-stimulated TNF\u03b1 autocrine/paracrine loop by the TNF\u03b1-blocking antibody Enbrel or by knockdown of TNFR1 abrogates BV6-induced cell elongation, migration and invasion. By demonstrating that the Smac mimetic BV6 at non-toxic concentrations promotes migration and invasion of GBM cells via non-canonical NF-\u03baB signaling, our findings have important implications for the use of Smac mimetics as cancer therapeutics.", 
        "genre": "research_article", 
        "id": "sg:pub.10.1038/cddis.2013.70", 
        "inLanguage": [
          "en"
        ], 
        "isAccessibleForFree": true, 
        "isPartOf": [
          {
            "id": "sg:journal.1042939", 
            "issn": [
              "2041-4889"
            ], 
            "name": "Cell Death & Disease", 
            "type": "Periodical"
          }, 
          {
            "issueNumber": "3", 
            "type": "PublicationIssue"
          }, 
          {
            "type": "PublicationVolume", 
            "volumeNumber": "4"
          }
        ], 
        "name": "Identification of non-canonical NF-\u03baB signaling as a critical mediator of Smac mimetic-stimulated migration and invasion of glioblastoma cells", 
        "pagination": "e564", 
        "productId": [
          {
            "name": "readcube_id", 
            "type": "PropertyValue", 
            "value": [
              "2288ded16891029b26a5b40c9012ed2abe130baaeeef567bcb13ad14b4f3d65d"
            ]
          }, 
          {
            "name": "pubmed_id", 
            "type": "PropertyValue", 
            "value": [
              "23538445"
            ]
          }, 
          {
            "name": "nlm_unique_id", 
            "type": "PropertyValue", 
            "value": [
              "101524092"
            ]
          }, 
          {
            "name": "doi", 
            "type": "PropertyValue", 
            "value": [
              "10.1038/cddis.2013.70"
            ]
          }, 
          {
            "name": "dimensions_id", 
            "type": "PropertyValue", 
            "value": [
              "pub.1007250168"
            ]
          }
        ], 
        "sameAs": [
          "https://doi.org/10.1038/cddis.2013.70", 
          "https://app.dimensions.ai/details/publication/pub.1007250168"
        ], 
        "sdDataset": "articles", 
        "sdDatePublished": "2019-04-10T23:13", 
        "sdLicense": "https://scigraph.springernature.com/explorer/license/", 
        "sdPublisher": {
          "name": "Springer Nature - SN SciGraph project", 
          "type": "Organization"
        }, 
        "sdSource": "s3://com-uberresearch-data-dimensions-target-20181106-alternative/cleanup/v134/2549eaecd7973599484d7c17b260dba0a4ecb94b/merge/v9/a6c9fde33151104705d4d7ff012ea9563521a3ce/jats-lookup/v90/0000000001_0000000264/records_8693_00000434.jsonl", 
        "type": "ScholarlyArticle", 
        "url": "https://www.nature.com/articles/cddis201370"
      }
    ]
     

    Download the RDF metadata as:  json-ld nt turtle xml License info

    HOW TO GET THIS DATA PROGRAMMATICALLY:

    JSON-LD is a popular format for linked data which is fully compatible with JSON.

    curl -H 'Accept: application/ld+json' 'https://scigraph.springernature.com/pub.10.1038/cddis.2013.70'

    N-Triples is a line-based linked data format ideal for batch operations.

    curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1038/cddis.2013.70'

    Turtle is a human-readable linked data format.

    curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1038/cddis.2013.70'

    RDF/XML is a standard XML format for linked data.

    curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1038/cddis.2013.70'


     

    This table displays all metadata directly associated to this object as RDF triples.

    337 TRIPLES      21 PREDICATES      97 URIs      41 LITERALS      29 BLANK NODES

    Subject Predicate Object
    1 sg:pub.10.1038/cddis.2013.70 schema:about N0837bbf1d6ea45ac9ffb823617d5a45d
    2 N18fb5d312cc3492c9a1b4aee5e3d1818
    3 N1db5cf0d0fcf4d55a0d0f244f14da885
    4 N1e06b929753643579202f7e350a2709f
    5 N3cff0c9bb6864cabbe72da2f4bf65295
    6 N4ab56b7f6cf94d5a9e12250b477c7412
    7 N4d15a0c57ead42deaf7ed05db57d3d3b
    8 N54abd728c5384e11ba8671b6c05ac5d6
    9 N5ab7def0e01f46818bdd01fbce5dd2a8
    10 N5b25acffdd21409a9d4a515e951afb65
    11 N5b669b007b694be0af0befbe0c48e157
    12 N86b07a93f3d34c92846281d39025ddc8
    13 N8fde68b9708d425ab03819f3130cc307
    14 N90c2867f16da4c64906d8d44c3575abb
    15 Na647cb8f42bc4d028298080135b74f96
    16 Na8e27343f7a046708450c1f05e9431ee
    17 Ncdf4641607e547fdb58a46b5bdc95167
    18 Nd3a89928eab1409e93b03f240454389c
    19 Nd540b6d607b74b6681cc95b1fd8a1415
    20 Ne9c25783233644d5802d73fcc4bd4072
    21 anzsrc-for:06
    22 anzsrc-for:0601
    23 schema:author N1e47568600c045d98ec6087ed2ff7289
    24 schema:citation sg:pub.10.1007/s00401-007-0293-7
    25 sg:pub.10.1007/s10014-005-0186-1
    26 sg:pub.10.1007/s10719-006-7927-1
    27 sg:pub.10.1007/s11060-007-9390-7
    28 sg:pub.10.1038/cdd.2012.10
    29 sg:pub.10.1038/ncb1804
    30 sg:pub.10.1038/ni.1676
    31 sg:pub.10.1038/ni.1678
    32 sg:pub.10.1038/ni.2065
    33 sg:pub.10.1038/nm735
    34 sg:pub.10.1038/nrd3627
    35 sg:pub.10.1038/onc.2009.161
    36 sg:pub.10.1038/onc.2012.108
    37 sg:pub.10.1038/sj.bjc.6605530
    38 sg:pub.10.1038/sj.cdd.4400503
    39 sg:pub.10.1038/sj.onc.1204868
    40 sg:pub.10.1038/sj.onc.1208842
    41 sg:pub.10.1038/sj.onc.1209776
    42 https://app.dimensions.ai/details/publication/pub.1082862824
    43 https://app.dimensions.ai/details/publication/pub.1083167141
    44 https://doi.org/10.1002/hep.22393
    45 https://doi.org/10.1002/ijc.22729
    46 https://doi.org/10.1016/j.ccr.2009.11.021
    47 https://doi.org/10.1016/j.cell.2007.10.030
    48 https://doi.org/10.1016/j.cell.2007.10.037
    49 https://doi.org/10.1016/j.molcel.2008.05.014
    50 https://doi.org/10.1016/j.molcel.2011.04.008
    51 https://doi.org/10.1016/s0092-8674(00)00008-8
    52 https://doi.org/10.1016/s0092-8674(00)00009-x
    53 https://doi.org/10.1038/emboj.2011.423
    54 https://doi.org/10.1038/sj.embor.7400795
    55 https://doi.org/10.1073/pnas.95.7.3792
    56 https://doi.org/10.1074/jbc.c800128200
    57 https://doi.org/10.1074/jbc.m110.176982
    58 https://doi.org/10.1074/jbc.m110.216226
    59 https://doi.org/10.1111/j.1582-4934.2009.00888.x
    60 https://doi.org/10.1126/science.278.5339.866
    61 https://doi.org/10.1128/mcb.14.12.7695
    62 https://doi.org/10.1152/ajpheart.00180.2010
    63 https://doi.org/10.1158/0008-5472.can-07-5173
    64 https://doi.org/10.1158/1078-0432.ccr-11-0075
    65 https://doi.org/10.1158/1535-7163.mct-11-0218
    66 https://doi.org/10.1200/jco.20.4.1063
    67 https://doi.org/10.1200/jco.2003.05.063
    68 https://doi.org/10.1242/jcs.075770
    69 https://doi.org/10.1593/neo.09436
    70 https://doi.org/10.4049/jimmunol.0903131
    71 https://doi.org/10.4049/jimmunol.1102454
    72 schema:datePublished 2013-03
    73 schema:datePublishedReg 2013-03-01
    74 schema:description As inhibitor of apoptosis (IAP) proteins can regulate additional signaling pathways beyond apoptosis, we investigated the effect of the second mitochondrial activator of caspases (Smac) mimetic BV6, which antagonizes IAP proteins, on non-apoptotic functions in glioblastoma (GBM). Here, we identify non-canonical nuclear factor-κB (NF-κB) signaling and a tumor necrosis factor-α (TNFα)/TNF receptor 1 (TNFR1) autocrine/paracrine loop as critical mediators of BV6-stimulated migration and invasion of GBM cells. In addition to GBM cell lines, BV6 triggers cell elongation, migration and invasion in primary, patient-derived GBM cells at non-toxic concentrations, which do not affect cell viability or proliferation, and also increases infiltrative tumor growth in vivo underscoring the relevance of these findings. Molecular studies reveal that BV6 causes rapid degradation of cellular IAP proteins, accumulation of NIK, processing of p100 to p52, translocation of p52 into the nucleus, increased NF-κB DNA binding and enhanced NF-κB transcriptional activity. Electrophoretic mobility shift assay supershift shows that the NF-κB DNA-binding subunits consist of p50, p52 and RelB further confirming the activation of the non-canonical NF-κB pathway. BV6-stimulated NF-κB activation leads to elevated mRNA levels of TNFα and additional NF-κB target genes involved in migration (i.e., interleukin 8, monocyte chemoattractant protein 1, CXC chemokine receptor 4) and invasion (i.e., matrix metalloproteinase-9). Importantly, inhibition of NF-κB by overexpression of dominant-negative IκBα superrepressor prevents the BV6-stimulated cell elongation, migration and invasion. Similarly, specific inhibition of non-canonical NF-κB signaling by RNA interference-mediated silencing of NIK suppresses the BV6-induced cell elongation, migration and invasion as well as upregulation of NF-κB target genes. Intriguingly, pharmacological or genetic inhibition of the BV6-stimulated TNFα autocrine/paracrine loop by the TNFα-blocking antibody Enbrel or by knockdown of TNFR1 abrogates BV6-induced cell elongation, migration and invasion. By demonstrating that the Smac mimetic BV6 at non-toxic concentrations promotes migration and invasion of GBM cells via non-canonical NF-κB signaling, our findings have important implications for the use of Smac mimetics as cancer therapeutics.
    75 schema:genre research_article
    76 schema:inLanguage en
    77 schema:isAccessibleForFree true
    78 schema:isPartOf N836c921ce3564e26b05bb2400660e871
    79 N98d45f0b0d5b494ab236671389b1f545
    80 sg:journal.1042939
    81 schema:name Identification of non-canonical NF-κB signaling as a critical mediator of Smac mimetic-stimulated migration and invasion of glioblastoma cells
    82 schema:pagination e564
    83 schema:productId N189d0f66bdf74606a2ac19dcdcb189cb
    84 N4ea3d612522047dd8284a1fc5b74c7e5
    85 N757fb9417c014816869b28c94297ca2d
    86 Ncbbfa4e6c15b42b6b0353d5009cc627d
    87 Nde0bc9ec1c05421b86c4226870ca5a6b
    88 schema:sameAs https://app.dimensions.ai/details/publication/pub.1007250168
    89 https://doi.org/10.1038/cddis.2013.70
    90 schema:sdDatePublished 2019-04-10T23:13
    91 schema:sdLicense https://scigraph.springernature.com/explorer/license/
    92 schema:sdPublisher N002c2c94cdfc457d81f485e8f2964578
    93 schema:url https://www.nature.com/articles/cddis201370
    94 sgo:license sg:explorer/license/
    95 sgo:sdDataset articles
    96 rdf:type schema:ScholarlyArticle
    97 N002c2c94cdfc457d81f485e8f2964578 schema:name Springer Nature - SN SciGraph project
    98 rdf:type schema:Organization
    99 N0837bbf1d6ea45ac9ffb823617d5a45d schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    100 schema:name RNA, Small Interfering
    101 rdf:type schema:DefinedTerm
    102 N0f0f366f49174626a8ee69f298696465 rdf:first sg:person.01017251224.26
    103 rdf:rest Ne7581cbb2239452f8cc7db3a452ed9af
    104 N189d0f66bdf74606a2ac19dcdcb189cb schema:name pubmed_id
    105 schema:value 23538445
    106 rdf:type schema:PropertyValue
    107 N18fb5d312cc3492c9a1b4aee5e3d1818 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    108 schema:name Mitochondrial Proteins
    109 rdf:type schema:DefinedTerm
    110 N1db5cf0d0fcf4d55a0d0f244f14da885 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    111 schema:name Signal Transduction
    112 rdf:type schema:DefinedTerm
    113 N1e06b929753643579202f7e350a2709f schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    114 schema:name Brain Neoplasms
    115 rdf:type schema:DefinedTerm
    116 N1e47568600c045d98ec6087ed2ff7289 rdf:first sg:person.01203762303.45
    117 rdf:rest Nc13497d948f04b70bbff3d67c3a52af7
    118 N3cff0c9bb6864cabbe72da2f4bf65295 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    119 schema:name Receptors, Tumor Necrosis Factor, Type I
    120 rdf:type schema:DefinedTerm
    121 N4ab56b7f6cf94d5a9e12250b477c7412 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    122 schema:name Tumor Necrosis Factor-alpha
    123 rdf:type schema:DefinedTerm
    124 N4d15a0c57ead42deaf7ed05db57d3d3b schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    125 schema:name Cell Line, Tumor
    126 rdf:type schema:DefinedTerm
    127 N4ea3d612522047dd8284a1fc5b74c7e5 schema:name nlm_unique_id
    128 schema:value 101524092
    129 rdf:type schema:PropertyValue
    130 N54abd728c5384e11ba8671b6c05ac5d6 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    131 schema:name Receptors, Tumor Necrosis Factor
    132 rdf:type schema:DefinedTerm
    133 N5ab7def0e01f46818bdd01fbce5dd2a8 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    134 schema:name Humans
    135 rdf:type schema:DefinedTerm
    136 N5b25acffdd21409a9d4a515e951afb65 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    137 schema:name Protein Subunits
    138 rdf:type schema:DefinedTerm
    139 N5b669b007b694be0af0befbe0c48e157 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    140 schema:name Gene Expression Regulation, Neoplastic
    141 rdf:type schema:DefinedTerm
    142 N757fb9417c014816869b28c94297ca2d schema:name doi
    143 schema:value 10.1038/cddis.2013.70
    144 rdf:type schema:PropertyValue
    145 N836c921ce3564e26b05bb2400660e871 schema:issueNumber 3
    146 rdf:type schema:PublicationIssue
    147 N86b07a93f3d34c92846281d39025ddc8 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    148 schema:name Cell Movement
    149 rdf:type schema:DefinedTerm
    150 N8fde68b9708d425ab03819f3130cc307 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    151 schema:name Peptidomimetics
    152 rdf:type schema:DefinedTerm
    153 N90c2867f16da4c64906d8d44c3575abb schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    154 schema:name Inhibitor of Apoptosis Proteins
    155 rdf:type schema:DefinedTerm
    156 N98d45f0b0d5b494ab236671389b1f545 schema:volumeNumber 4
    157 rdf:type schema:PublicationVolume
    158 Na647cb8f42bc4d028298080135b74f96 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    159 schema:name Immunoglobulin G
    160 rdf:type schema:DefinedTerm
    161 Na8e27343f7a046708450c1f05e9431ee schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    162 schema:name Neoplasm Invasiveness
    163 rdf:type schema:DefinedTerm
    164 Nabb0d4eb52ed4c1bb8225d227d0b9889 rdf:first sg:person.01331656400.85
    165 rdf:rest rdf:nil
    166 Nc13497d948f04b70bbff3d67c3a52af7 rdf:first sg:person.01220446253.14
    167 rdf:rest N0f0f366f49174626a8ee69f298696465
    168 Ncbbfa4e6c15b42b6b0353d5009cc627d schema:name readcube_id
    169 schema:value 2288ded16891029b26a5b40c9012ed2abe130baaeeef567bcb13ad14b4f3d65d
    170 rdf:type schema:PropertyValue
    171 Ncdf4641607e547fdb58a46b5bdc95167 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    172 schema:name NF-kappa B
    173 rdf:type schema:DefinedTerm
    174 Nd3a89928eab1409e93b03f240454389c schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    175 schema:name Etanercept
    176 rdf:type schema:DefinedTerm
    177 Nd540b6d607b74b6681cc95b1fd8a1415 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    178 schema:name Glioblastoma
    179 rdf:type schema:DefinedTerm
    180 Nde0bc9ec1c05421b86c4226870ca5a6b schema:name dimensions_id
    181 schema:value pub.1007250168
    182 rdf:type schema:PropertyValue
    183 Ne7581cbb2239452f8cc7db3a452ed9af rdf:first sg:person.01152534517.15
    184 rdf:rest Nabb0d4eb52ed4c1bb8225d227d0b9889
    185 Ne9c25783233644d5802d73fcc4bd4072 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    186 schema:name Intracellular Signaling Peptides and Proteins
    187 rdf:type schema:DefinedTerm
    188 anzsrc-for:06 schema:inDefinedTermSet anzsrc-for:
    189 schema:name Biological Sciences
    190 rdf:type schema:DefinedTerm
    191 anzsrc-for:0601 schema:inDefinedTermSet anzsrc-for:
    192 schema:name Biochemistry and Cell Biology
    193 rdf:type schema:DefinedTerm
    194 sg:journal.1042939 schema:issn 2041-4889
    195 schema:name Cell Death & Disease
    196 rdf:type schema:Periodical
    197 sg:person.01017251224.26 schema:affiliation https://www.grid.ac/institutes/grid.7839.5
    198 schema:familyName Eckhardt
    199 schema:givenName I
    200 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01017251224.26
    201 rdf:type schema:Person
    202 sg:person.01152534517.15 schema:affiliation https://www.grid.ac/institutes/grid.7839.5
    203 schema:familyName Rajalingam
    204 schema:givenName K
    205 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01152534517.15
    206 rdf:type schema:Person
    207 sg:person.01203762303.45 schema:affiliation https://www.grid.ac/institutes/grid.7839.5
    208 schema:familyName Tchoghandjian
    209 schema:givenName A
    210 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01203762303.45
    211 rdf:type schema:Person
    212 sg:person.01220446253.14 schema:affiliation https://www.grid.ac/institutes/grid.7839.5
    213 schema:familyName Jennewein
    214 schema:givenName C
    215 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01220446253.14
    216 rdf:type schema:Person
    217 sg:person.01331656400.85 schema:affiliation https://www.grid.ac/institutes/grid.7839.5
    218 schema:familyName Fulda
    219 schema:givenName S
    220 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01331656400.85
    221 rdf:type schema:Person
    222 sg:pub.10.1007/s00401-007-0293-7 schema:sameAs https://app.dimensions.ai/details/publication/pub.1019580592
    223 https://doi.org/10.1007/s00401-007-0293-7
    224 rdf:type schema:CreativeWork
    225 sg:pub.10.1007/s10014-005-0186-1 schema:sameAs https://app.dimensions.ai/details/publication/pub.1045630891
    226 https://doi.org/10.1007/s10014-005-0186-1
    227 rdf:type schema:CreativeWork
    228 sg:pub.10.1007/s10719-006-7927-1 schema:sameAs https://app.dimensions.ai/details/publication/pub.1040188397
    229 https://doi.org/10.1007/s10719-006-7927-1
    230 rdf:type schema:CreativeWork
    231 sg:pub.10.1007/s11060-007-9390-7 schema:sameAs https://app.dimensions.ai/details/publication/pub.1046986451
    232 https://doi.org/10.1007/s11060-007-9390-7
    233 rdf:type schema:CreativeWork
    234 sg:pub.10.1038/cdd.2012.10 schema:sameAs https://app.dimensions.ai/details/publication/pub.1016341290
    235 https://doi.org/10.1038/cdd.2012.10
    236 rdf:type schema:CreativeWork
    237 sg:pub.10.1038/ncb1804 schema:sameAs https://app.dimensions.ai/details/publication/pub.1017925206
    238 https://doi.org/10.1038/ncb1804
    239 rdf:type schema:CreativeWork
    240 sg:pub.10.1038/ni.1676 schema:sameAs https://app.dimensions.ai/details/publication/pub.1053487240
    241 https://doi.org/10.1038/ni.1676
    242 rdf:type schema:CreativeWork
    243 sg:pub.10.1038/ni.1678 schema:sameAs https://app.dimensions.ai/details/publication/pub.1017708694
    244 https://doi.org/10.1038/ni.1678
    245 rdf:type schema:CreativeWork
    246 sg:pub.10.1038/ni.2065 schema:sameAs https://app.dimensions.ai/details/publication/pub.1006965315
    247 https://doi.org/10.1038/ni.2065
    248 rdf:type schema:CreativeWork
    249 sg:pub.10.1038/nm735 schema:sameAs https://app.dimensions.ai/details/publication/pub.1020239862
    250 https://doi.org/10.1038/nm735
    251 rdf:type schema:CreativeWork
    252 sg:pub.10.1038/nrd3627 schema:sameAs https://app.dimensions.ai/details/publication/pub.1025792112
    253 https://doi.org/10.1038/nrd3627
    254 rdf:type schema:CreativeWork
    255 sg:pub.10.1038/onc.2009.161 schema:sameAs https://app.dimensions.ai/details/publication/pub.1028121111
    256 https://doi.org/10.1038/onc.2009.161
    257 rdf:type schema:CreativeWork
    258 sg:pub.10.1038/onc.2012.108 schema:sameAs https://app.dimensions.ai/details/publication/pub.1050959459
    259 https://doi.org/10.1038/onc.2012.108
    260 rdf:type schema:CreativeWork
    261 sg:pub.10.1038/sj.bjc.6605530 schema:sameAs https://app.dimensions.ai/details/publication/pub.1017883550
    262 https://doi.org/10.1038/sj.bjc.6605530
    263 rdf:type schema:CreativeWork
    264 sg:pub.10.1038/sj.cdd.4400503 schema:sameAs https://app.dimensions.ai/details/publication/pub.1042692074
    265 https://doi.org/10.1038/sj.cdd.4400503
    266 rdf:type schema:CreativeWork
    267 sg:pub.10.1038/sj.onc.1204868 schema:sameAs https://app.dimensions.ai/details/publication/pub.1045634373
    268 https://doi.org/10.1038/sj.onc.1204868
    269 rdf:type schema:CreativeWork
    270 sg:pub.10.1038/sj.onc.1208842 schema:sameAs https://app.dimensions.ai/details/publication/pub.1036583697
    271 https://doi.org/10.1038/sj.onc.1208842
    272 rdf:type schema:CreativeWork
    273 sg:pub.10.1038/sj.onc.1209776 schema:sameAs https://app.dimensions.ai/details/publication/pub.1001145043
    274 https://doi.org/10.1038/sj.onc.1209776
    275 rdf:type schema:CreativeWork
    276 https://app.dimensions.ai/details/publication/pub.1082862824 schema:CreativeWork
    277 https://app.dimensions.ai/details/publication/pub.1083167141 schema:CreativeWork
    278 https://doi.org/10.1002/hep.22393 schema:sameAs https://app.dimensions.ai/details/publication/pub.1026491192
    279 rdf:type schema:CreativeWork
    280 https://doi.org/10.1002/ijc.22729 schema:sameAs https://app.dimensions.ai/details/publication/pub.1024107340
    281 rdf:type schema:CreativeWork
    282 https://doi.org/10.1016/j.ccr.2009.11.021 schema:sameAs https://app.dimensions.ai/details/publication/pub.1008831547
    283 rdf:type schema:CreativeWork
    284 https://doi.org/10.1016/j.cell.2007.10.030 schema:sameAs https://app.dimensions.ai/details/publication/pub.1036164945
    285 rdf:type schema:CreativeWork
    286 https://doi.org/10.1016/j.cell.2007.10.037 schema:sameAs https://app.dimensions.ai/details/publication/pub.1032826025
    287 rdf:type schema:CreativeWork
    288 https://doi.org/10.1016/j.molcel.2008.05.014 schema:sameAs https://app.dimensions.ai/details/publication/pub.1027166093
    289 rdf:type schema:CreativeWork
    290 https://doi.org/10.1016/j.molcel.2011.04.008 schema:sameAs https://app.dimensions.ai/details/publication/pub.1037526336
    291 rdf:type schema:CreativeWork
    292 https://doi.org/10.1016/s0092-8674(00)00008-8 schema:sameAs https://app.dimensions.ai/details/publication/pub.1033773534
    293 rdf:type schema:CreativeWork
    294 https://doi.org/10.1016/s0092-8674(00)00009-x schema:sameAs https://app.dimensions.ai/details/publication/pub.1021931408
    295 rdf:type schema:CreativeWork
    296 https://doi.org/10.1038/emboj.2011.423 schema:sameAs https://app.dimensions.ai/details/publication/pub.1030004367
    297 rdf:type schema:CreativeWork
    298 https://doi.org/10.1038/sj.embor.7400795 schema:sameAs https://app.dimensions.ai/details/publication/pub.1006661587
    299 rdf:type schema:CreativeWork
    300 https://doi.org/10.1073/pnas.95.7.3792 schema:sameAs https://app.dimensions.ai/details/publication/pub.1000474592
    301 rdf:type schema:CreativeWork
    302 https://doi.org/10.1074/jbc.c800128200 schema:sameAs https://app.dimensions.ai/details/publication/pub.1024459927
    303 rdf:type schema:CreativeWork
    304 https://doi.org/10.1074/jbc.m110.176982 schema:sameAs https://app.dimensions.ai/details/publication/pub.1051563020
    305 rdf:type schema:CreativeWork
    306 https://doi.org/10.1074/jbc.m110.216226 schema:sameAs https://app.dimensions.ai/details/publication/pub.1009588501
    307 rdf:type schema:CreativeWork
    308 https://doi.org/10.1111/j.1582-4934.2009.00888.x schema:sameAs https://app.dimensions.ai/details/publication/pub.1015845763
    309 rdf:type schema:CreativeWork
    310 https://doi.org/10.1126/science.278.5339.866 schema:sameAs https://app.dimensions.ai/details/publication/pub.1062558523
    311 rdf:type schema:CreativeWork
    312 https://doi.org/10.1128/mcb.14.12.7695 schema:sameAs https://app.dimensions.ai/details/publication/pub.1024709479
    313 rdf:type schema:CreativeWork
    314 https://doi.org/10.1152/ajpheart.00180.2010 schema:sameAs https://app.dimensions.ai/details/publication/pub.1019966031
    315 rdf:type schema:CreativeWork
    316 https://doi.org/10.1158/0008-5472.can-07-5173 schema:sameAs https://app.dimensions.ai/details/publication/pub.1034206312
    317 rdf:type schema:CreativeWork
    318 https://doi.org/10.1158/1078-0432.ccr-11-0075 schema:sameAs https://app.dimensions.ai/details/publication/pub.1043146275
    319 rdf:type schema:CreativeWork
    320 https://doi.org/10.1158/1535-7163.mct-11-0218 schema:sameAs https://app.dimensions.ai/details/publication/pub.1053405385
    321 rdf:type schema:CreativeWork
    322 https://doi.org/10.1200/jco.20.4.1063 schema:sameAs https://app.dimensions.ai/details/publication/pub.1064202816
    323 rdf:type schema:CreativeWork
    324 https://doi.org/10.1200/jco.2003.05.063 schema:sameAs https://app.dimensions.ai/details/publication/pub.1064203593
    325 rdf:type schema:CreativeWork
    326 https://doi.org/10.1242/jcs.075770 schema:sameAs https://app.dimensions.ai/details/publication/pub.1043720963
    327 rdf:type schema:CreativeWork
    328 https://doi.org/10.1593/neo.09436 schema:sameAs https://app.dimensions.ai/details/publication/pub.1006077979
    329 rdf:type schema:CreativeWork
    330 https://doi.org/10.4049/jimmunol.0903131 schema:sameAs https://app.dimensions.ai/details/publication/pub.1025846006
    331 rdf:type schema:CreativeWork
    332 https://doi.org/10.4049/jimmunol.1102454 schema:sameAs https://app.dimensions.ai/details/publication/pub.1033171277
    333 rdf:type schema:CreativeWork
    334 https://www.grid.ac/institutes/grid.7839.5 schema:alternateName Goethe University Frankfurt
    335 schema:name Emmy Noether Group of the DFG, Institute of Biochemistry II, Goethe University Medical School, Frankfurt, Germany
    336 Institute for Experimental Cancer Research in Pediatrics, Goethe University, Frankfurt, Germany
    337 rdf:type schema:Organization
     




    Preview window. Press ESC to close (or click here)


    ...