Mutant B-RAF-Mcl-1 survival signaling depends on the STAT3 transcription factor View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2013-03-04

AUTHORS

T M Becker, S C Boyd, B Mijatov, K Gowrishankar, S Snoyman, G M Pupo, R A Scolyer, G J Mann, R F Kefford, X D Zhang, H Rizos

ABSTRACT

Approximately 50% of melanomas depend on mutant B-RAF for proliferation, metastasis and survival. The inhibition of oncogenic B-RAF with highly targeted compounds has produced remarkable albeit short-lived clinical responses in B-RAF mutant melanoma patients. Reactivation of signaling downstream of B-RAF is frequently associated with acquired resistance to B-RAF inhibitors, and the identification of B-RAF targets may provide new strategies for managing melanoma. Oncogenic B-RAFV600E is known to promote the stabilizing phosphorylation of the anti-apoptotic protein Mcl-1, implicated in melanoma survival and chemoresistance. We now show that B-RAFV600E signaling also induces the transcription of Mcl-1 in melanocytes and melanoma. We demonstrate that activation of STAT3 serine-727 and tyrosine-705 phosphorylations is promoted by B-RAFV600E activity and that the Mcl-1 promoter is dependent on a STAT consensus-site for B-RAF-mediated activation. Consequently, suppression of STAT3 activity disrupted B-RAFV600E-mediated induction of Mcl-1 and reduced melanoma cell survival. We propose that STAT3 has a central role in the survival and contributes to chemoresistance of B-RAFV600E melanoma. More... »

PAGES

1158-1166

References to SciGraph publications

  • 2009-01-12. The STAT3 inhibitor NSC 74859 is effective in hepatocellular cancers with disrupted TGF-β signaling in ONCOGENE
  • 2006-03-06. Autocrine IL-6-induced Stat3 activation contributes to the pathogenesis of lung adenocarcinoma and malignant pleural effusion in ONCOGENE
  • 2005-06. Targeting STAT3 affects melanoma on multiple fronts in CANCER AND METASTASIS REVIEWS
  • 2005-08. BRAFE600-associated senescence-like cell cycle arrest of human naevi in NATURE
  • 2010-06-25. The small molecule curcumin analog FLLL32 induces apoptosis in melanoma cells via STAT3 inhibition and retains the cellular response to cytokines with anti-tumor activity in MOLECULAR CANCER
  • 2004-02. The STATs of cancer — new molecular targets come of age in NATURE REVIEWS CANCER
  • 2010-03-24. B-RAF Inhibitors: An Evolving Role in the Therapy of Malignant Melanoma in CURRENT ONCOLOGY REPORTS
  • 2002-09-01. STATs: transcriptional control and biological impact in NATURE REVIEWS MOLECULAR CELL BIOLOGY
  • 2007-03-26. Mcl-1, Bcl-XL and Stat3 expression are associated with progression of melanoma whereas Bcl-2, AP-2 and MITF levels decrease during progression of melanoma in MODERN PATHOLOGY
  • 2008-12-16. Mcl-1 is a potential therapeutic target in multiple types of cancer in CELLULAR AND MOLECULAR LIFE SCIENCES
  • 2009-01-06. LLL-3 inhibits STAT3 activity, suppresses glioblastoma cell growth and prolongs survival in a mouse glioblastoma model in BRITISH JOURNAL OF CANCER
  • 2010-08-16. A novel small molecule inhibits STAT3 phosphorylation and DNA binding activity and exhibits potent growth suppressive activity in human cancer cells in MOLECULAR CANCER
  • 2010-05-11. STAT3 inhibitor WP1066 as a novel therapeutic agent for renal cell carcinoma in BRITISH JOURNAL OF CANCER
  • 2010-09-02. Apoptosis of human melanoma cells induced by inhibition of B-RAFV600E involves preferential splicing of bimS in CELL DEATH & DISEASE
  • 2002-10-09. Roles of activated Src and Stat3 signaling in melanoma tumor cell growth in ONCOGENE
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/onc.2013.45

    DOI

    http://dx.doi.org/10.1038/onc.2013.45

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1002813670

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/23455323


    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/2008/11", 
            "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
            "name": "Medical and Health Sciences", 
            "type": "DefinedTerm"
          }, 
          {
            "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/1112", 
            "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
            "name": "Oncology and Carcinogenesis", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Cell Line, Tumor", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Cell Survival", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Humans", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Interleukin-6", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Melanocytes", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Melanoma", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Mutation", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Myeloid Cell Leukemia Sequence 1 Protein", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Phosphorylation", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Promoter Regions, Genetic", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Proto-Oncogene Proteins B-raf", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "STAT3 Transcription Factor", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Signal Transduction", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Transcription Factors", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Transcriptional Activation", 
            "type": "DefinedTerm"
          }
        ], 
        "author": [
          {
            "affiliation": {
              "alternateName": "Westmead Institute for Cancer Research, University of Sydney at Westmead Millennium Institute, Westmead Hospital, Sydney, New South Wales, Australia", 
              "id": "http://www.grid.ac/institutes/grid.413252.3", 
              "name": [
                "Westmead Institute for Cancer Research, University of Sydney at Westmead Millennium Institute, Westmead Hospital, Sydney, New South Wales, Australia"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Becker", 
            "givenName": "T M", 
            "id": "sg:person.01332124207.92", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01332124207.92"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Westmead Institute for Cancer Research, University of Sydney at Westmead Millennium Institute, Westmead Hospital, Sydney, New South Wales, Australia", 
              "id": "http://www.grid.ac/institutes/grid.413252.3", 
              "name": [
                "Westmead Institute for Cancer Research, University of Sydney at Westmead Millennium Institute, Westmead Hospital, Sydney, New South Wales, Australia"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Boyd", 
            "givenName": "S C", 
            "id": "sg:person.01023612122.13", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01023612122.13"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Westmead Institute for Cancer Research, University of Sydney at Westmead Millennium Institute, Westmead Hospital, Sydney, New South Wales, Australia", 
              "id": "http://www.grid.ac/institutes/grid.413252.3", 
              "name": [
                "Westmead Institute for Cancer Research, University of Sydney at Westmead Millennium Institute, Westmead Hospital, Sydney, New South Wales, Australia"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Mijatov", 
            "givenName": "B", 
            "id": "sg:person.01140040522.17", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01140040522.17"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Westmead Institute for Cancer Research, University of Sydney at Westmead Millennium Institute, Westmead Hospital, Sydney, New South Wales, Australia", 
              "id": "http://www.grid.ac/institutes/grid.413252.3", 
              "name": [
                "Westmead Institute for Cancer Research, University of Sydney at Westmead Millennium Institute, Westmead Hospital, Sydney, New South Wales, Australia"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Gowrishankar", 
            "givenName": "K", 
            "id": "sg:person.01125632101.34", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01125632101.34"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Westmead Institute for Cancer Research, University of Sydney at Westmead Millennium Institute, Westmead Hospital, Sydney, New South Wales, Australia", 
              "id": "http://www.grid.ac/institutes/grid.413252.3", 
              "name": [
                "Westmead Institute for Cancer Research, University of Sydney at Westmead Millennium Institute, Westmead Hospital, Sydney, New South Wales, Australia"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Snoyman", 
            "givenName": "S", 
            "id": "sg:person.01173745301.12", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01173745301.12"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Westmead Institute for Cancer Research, University of Sydney at Westmead Millennium Institute, Westmead Hospital, Sydney, New South Wales, Australia", 
              "id": "http://www.grid.ac/institutes/grid.413252.3", 
              "name": [
                "Westmead Institute for Cancer Research, University of Sydney at Westmead Millennium Institute, Westmead Hospital, Sydney, New South Wales, Australia"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Pupo", 
            "givenName": "G M", 
            "id": "sg:person.0631770737.43", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0631770737.43"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Melanoma Institute Australia, Sydney, New South Wales, Australia", 
              "id": "http://www.grid.ac/institutes/grid.419690.3", 
              "name": [
                "Melanoma Institute Australia, Sydney, New South Wales, Australia"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Scolyer", 
            "givenName": "R A", 
            "id": "sg:person.01276020470.05", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01276020470.05"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Melanoma Institute Australia, Sydney, New South Wales, Australia", 
              "id": "http://www.grid.ac/institutes/grid.419690.3", 
              "name": [
                "Westmead Institute for Cancer Research, University of Sydney at Westmead Millennium Institute, Westmead Hospital, Sydney, New South Wales, Australia", 
                "Melanoma Institute Australia, Sydney, New South Wales, Australia"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Mann", 
            "givenName": "G J", 
            "id": "sg:person.013701550142.38", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.013701550142.38"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Melanoma Institute Australia, Sydney, New South Wales, Australia", 
              "id": "http://www.grid.ac/institutes/grid.419690.3", 
              "name": [
                "Westmead Institute for Cancer Research, University of Sydney at Westmead Millennium Institute, Westmead Hospital, Sydney, New South Wales, Australia", 
                "Melanoma Institute Australia, Sydney, New South Wales, Australia"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Kefford", 
            "givenName": "R F", 
            "id": "sg:person.0654633307.36", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0654633307.36"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Immunology and Oncology Unit, University of Newcastle, Newcastle, New South Wales, Australia", 
              "id": "http://www.grid.ac/institutes/grid.266842.c", 
              "name": [
                "Immunology and Oncology Unit, University of Newcastle, Newcastle, New South Wales, Australia"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Zhang", 
            "givenName": "X D", 
            "id": "sg:person.01210116316.18", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01210116316.18"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Westmead Institute for Cancer Research, University of Sydney at Westmead Millennium Institute, Westmead Hospital, Sydney, New South Wales, Australia", 
              "id": "http://www.grid.ac/institutes/grid.413252.3", 
              "name": [
                "Westmead Institute for Cancer Research, University of Sydney at Westmead Millennium Institute, Westmead Hospital, Sydney, New South Wales, Australia"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Rizos", 
            "givenName": "H", 
            "id": "sg:person.01101732762.50", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01101732762.50"
            ], 
            "type": "Person"
          }
        ], 
        "citation": [
          {
            "id": "sg:pub.10.1038/nature03890", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1003324113", 
              "https://doi.org/10.1038/nature03890"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nrm909", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1045111933", 
              "https://doi.org/10.1038/nrm909"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/modpathol.3800750", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1022673157", 
              "https://doi.org/10.1038/modpathol.3800750"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1186/1476-4598-9-165", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1048943178", 
              "https://doi.org/10.1186/1476-4598-9-165"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nrc1275", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1031068002", 
              "https://doi.org/10.1038/nrc1275"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/sj.onc.1205859", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1014860210", 
              "https://doi.org/10.1038/sj.onc.1205859"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1186/1476-4598-9-217", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1052907373", 
              "https://doi.org/10.1186/1476-4598-9-217"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/sj.bjc.6605691", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1012090202", 
              "https://doi.org/10.1038/sj.bjc.6605691"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/sj.onc.1209464", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1038055616", 
              "https://doi.org/10.1038/sj.onc.1209464"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/onc.2008.448", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1027217991", 
              "https://doi.org/10.1038/onc.2008.448"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1007/s11912-010-0095-2", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1003251632", 
              "https://doi.org/10.1007/s11912-010-0095-2"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/sj.bjc.6604793", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1028780915", 
              "https://doi.org/10.1038/sj.bjc.6604793"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1007/s10555-005-1580-1", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1047575709", 
              "https://doi.org/10.1007/s10555-005-1580-1"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/cddis.2010.48", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1005879650", 
              "https://doi.org/10.1038/cddis.2010.48"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1007/s00018-008-8637-6", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1023498818", 
              "https://doi.org/10.1007/s00018-008-8637-6"
            ], 
            "type": "CreativeWork"
          }
        ], 
        "datePublished": "2013-03-04", 
        "datePublishedReg": "2013-03-04", 
        "description": "Approximately 50% of melanomas depend on mutant B-RAF for proliferation, metastasis and survival. The inhibition of oncogenic B-RAF with highly targeted compounds has produced remarkable albeit short-lived clinical responses in B-RAF mutant melanoma patients. Reactivation of signaling downstream of B-RAF is frequently associated with acquired resistance to B-RAF inhibitors, and the identification of B-RAF targets may provide new strategies for managing melanoma. Oncogenic B-RAFV600E is known to promote the stabilizing phosphorylation of the anti-apoptotic protein Mcl-1, implicated in melanoma survival and chemoresistance. We now show that B-RAFV600E signaling also induces the transcription of Mcl-1 in melanocytes and melanoma. We demonstrate that activation of STAT3 serine-727 and tyrosine-705 phosphorylations is promoted by B-RAFV600E activity and that the Mcl-1 promoter is dependent on a STAT consensus-site for B-RAF-mediated activation. Consequently, suppression of STAT3 activity disrupted B-RAFV600E-mediated induction of Mcl-1 and reduced melanoma cell survival. We propose that STAT3 has a central role in the survival and contributes to chemoresistance of B-RAFV600E melanoma.", 
        "genre": "article", 
        "id": "sg:pub.10.1038/onc.2013.45", 
        "inLanguage": "en", 
        "isAccessibleForFree": false, 
        "isFundedItemOf": [
          {
            "id": "sg:grant.6713550", 
            "type": "MonetaryGrant"
          }
        ], 
        "isPartOf": [
          {
            "id": "sg:journal.1097543", 
            "issn": [
              "0950-9232", 
              "1476-5594"
            ], 
            "name": "Oncogene", 
            "publisher": "Springer Nature", 
            "type": "Periodical"
          }, 
          {
            "issueNumber": "9", 
            "type": "PublicationIssue"
          }, 
          {
            "type": "PublicationVolume", 
            "volumeNumber": "33"
          }
        ], 
        "keywords": [
          "B-Raf", 
          "Mcl-1", 
          "oncogenic B-Raf", 
          "B-RafV600E", 
          "tyrosine-705 phosphorylation", 
          "Mcl-1 promoter", 
          "anti-apoptotic protein Mcl-1", 
          "mutant B-RAF", 
          "oncogenic B-RafV600E", 
          "protein Mcl-1", 
          "melanoma cell survival", 
          "STAT3 transcription factor", 
          "serine 727", 
          "transcription factors", 
          "STAT3 activity", 
          "B-Raf inhibitors", 
          "cell survival", 
          "mutant melanoma patients", 
          "phosphorylation", 
          "central role", 
          "chemoresistance", 
          "activation", 
          "transcription", 
          "promoter", 
          "melanoma survival", 
          "survival", 
          "STAT", 
          "STAT3", 
          "melanocytes", 
          "new strategy", 
          "proliferation", 
          "activity", 
          "induction", 
          "inhibitors", 
          "inhibition", 
          "target", 
          "identification", 
          "melanoma", 
          "clinical response", 
          "melanoma patients", 
          "role", 
          "suppression", 
          "resistance", 
          "response", 
          "reactivation", 
          "metastasis", 
          "compounds", 
          "factors", 
          "patients", 
          "strategies"
        ], 
        "name": "Mutant B-RAF-Mcl-1 survival signaling depends on the STAT3 transcription factor", 
        "pagination": "1158-1166", 
        "productId": [
          {
            "name": "dimensions_id", 
            "type": "PropertyValue", 
            "value": [
              "pub.1002813670"
            ]
          }, 
          {
            "name": "doi", 
            "type": "PropertyValue", 
            "value": [
              "10.1038/onc.2013.45"
            ]
          }, 
          {
            "name": "pubmed_id", 
            "type": "PropertyValue", 
            "value": [
              "23455323"
            ]
          }
        ], 
        "sameAs": [
          "https://doi.org/10.1038/onc.2013.45", 
          "https://app.dimensions.ai/details/publication/pub.1002813670"
        ], 
        "sdDataset": "articles", 
        "sdDatePublished": "2022-06-01T22:12", 
        "sdLicense": "https://scigraph.springernature.com/explorer/license/", 
        "sdPublisher": {
          "name": "Springer Nature - SN SciGraph project", 
          "type": "Organization"
        }, 
        "sdSource": "s3://com-springernature-scigraph/baseset/20220601/entities/gbq_results/article/article_608.jsonl", 
        "type": "ScholarlyArticle", 
        "url": "https://doi.org/10.1038/onc.2013.45"
      }
    ]
     

    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/onc.2013.45'

    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/onc.2013.45'

    Turtle is a human-readable linked data format.

    curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1038/onc.2013.45'

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

    curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1038/onc.2013.45'


     

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

    311 TRIPLES      22 PREDICATES      106 URIs      83 LITERALS      22 BLANK NODES

    Subject Predicate Object
    1 sg:pub.10.1038/onc.2013.45 schema:about N041f87159dba4fe8a4bef27d3cc16f83
    2 N04c03d72cadf4c129d5623c40880b846
    3 N1308d1a4fd404b5aaa691d3f5cd8d54a
    4 N351f4c3c06514035bb9a9adff5143cc7
    5 N523e495158ca4cb6a5d343aaf415c869
    6 N63ac50719b27441e8dfcf00d8bb75ba3
    7 N69d52b507e90437f8911a7bc2d5d0e45
    8 N734087b0e25f45d4bd61d27a41f6b192
    9 N75a8f6b8b78949fc8f7f3a4ed9c654ba
    10 N76c873945a92449787cf6b674c30ea19
    11 N8b09df9aa37d4d32aba73a27a3d20c2e
    12 N8b74c47d560c47eaadb33f7224536551
    13 Nadcdcacc3f3c4fa68ab4346a67c12d1f
    14 Nf174469205c449bdbf8ab0373944fff6
    15 Nf54c4a76f7674d78ac2378c0979f63a7
    16 anzsrc-for:11
    17 anzsrc-for:1112
    18 schema:author N1e6bd46f310f489fbb6ad778df0a27d8
    19 schema:citation sg:pub.10.1007/s00018-008-8637-6
    20 sg:pub.10.1007/s10555-005-1580-1
    21 sg:pub.10.1007/s11912-010-0095-2
    22 sg:pub.10.1038/cddis.2010.48
    23 sg:pub.10.1038/modpathol.3800750
    24 sg:pub.10.1038/nature03890
    25 sg:pub.10.1038/nrc1275
    26 sg:pub.10.1038/nrm909
    27 sg:pub.10.1038/onc.2008.448
    28 sg:pub.10.1038/sj.bjc.6604793
    29 sg:pub.10.1038/sj.bjc.6605691
    30 sg:pub.10.1038/sj.onc.1205859
    31 sg:pub.10.1038/sj.onc.1209464
    32 sg:pub.10.1186/1476-4598-9-165
    33 sg:pub.10.1186/1476-4598-9-217
    34 schema:datePublished 2013-03-04
    35 schema:datePublishedReg 2013-03-04
    36 schema:description Approximately 50% of melanomas depend on mutant B-RAF for proliferation, metastasis and survival. The inhibition of oncogenic B-RAF with highly targeted compounds has produced remarkable albeit short-lived clinical responses in B-RAF mutant melanoma patients. Reactivation of signaling downstream of B-RAF is frequently associated with acquired resistance to B-RAF inhibitors, and the identification of B-RAF targets may provide new strategies for managing melanoma. Oncogenic B-RAFV600E is known to promote the stabilizing phosphorylation of the anti-apoptotic protein Mcl-1, implicated in melanoma survival and chemoresistance. We now show that B-RAFV600E signaling also induces the transcription of Mcl-1 in melanocytes and melanoma. We demonstrate that activation of STAT3 serine-727 and tyrosine-705 phosphorylations is promoted by B-RAFV600E activity and that the Mcl-1 promoter is dependent on a STAT consensus-site for B-RAF-mediated activation. Consequently, suppression of STAT3 activity disrupted B-RAFV600E-mediated induction of Mcl-1 and reduced melanoma cell survival. We propose that STAT3 has a central role in the survival and contributes to chemoresistance of B-RAFV600E melanoma.
    37 schema:genre article
    38 schema:inLanguage en
    39 schema:isAccessibleForFree false
    40 schema:isPartOf N19558fd34bb5477389ee59cf8dce62ce
    41 Ncea63fac66c34572847bb8e371b28078
    42 sg:journal.1097543
    43 schema:keywords B-Raf
    44 B-Raf inhibitors
    45 B-RafV600E
    46 Mcl-1
    47 Mcl-1 promoter
    48 STAT
    49 STAT3
    50 STAT3 activity
    51 STAT3 transcription factor
    52 activation
    53 activity
    54 anti-apoptotic protein Mcl-1
    55 cell survival
    56 central role
    57 chemoresistance
    58 clinical response
    59 compounds
    60 factors
    61 identification
    62 induction
    63 inhibition
    64 inhibitors
    65 melanocytes
    66 melanoma
    67 melanoma cell survival
    68 melanoma patients
    69 melanoma survival
    70 metastasis
    71 mutant B-RAF
    72 mutant melanoma patients
    73 new strategy
    74 oncogenic B-Raf
    75 oncogenic B-RafV600E
    76 patients
    77 phosphorylation
    78 proliferation
    79 promoter
    80 protein Mcl-1
    81 reactivation
    82 resistance
    83 response
    84 role
    85 serine 727
    86 strategies
    87 suppression
    88 survival
    89 target
    90 transcription
    91 transcription factors
    92 tyrosine-705 phosphorylation
    93 schema:name Mutant B-RAF-Mcl-1 survival signaling depends on the STAT3 transcription factor
    94 schema:pagination 1158-1166
    95 schema:productId N0e3489cec0fc420d9b60ce63060d53f7
    96 N84e9bafe3048466facdeeca5eb410728
    97 Nb10b91e229f1400d833487e5d02f28a1
    98 schema:sameAs https://app.dimensions.ai/details/publication/pub.1002813670
    99 https://doi.org/10.1038/onc.2013.45
    100 schema:sdDatePublished 2022-06-01T22:12
    101 schema:sdLicense https://scigraph.springernature.com/explorer/license/
    102 schema:sdPublisher N7223f5dde4d54e49bce9d2bec6775fb5
    103 schema:url https://doi.org/10.1038/onc.2013.45
    104 sgo:license sg:explorer/license/
    105 sgo:sdDataset articles
    106 rdf:type schema:ScholarlyArticle
    107 N041f87159dba4fe8a4bef27d3cc16f83 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    108 schema:name Transcriptional Activation
    109 rdf:type schema:DefinedTerm
    110 N04c03d72cadf4c129d5623c40880b846 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    111 schema:name Cell Line, Tumor
    112 rdf:type schema:DefinedTerm
    113 N0e3489cec0fc420d9b60ce63060d53f7 schema:name pubmed_id
    114 schema:value 23455323
    115 rdf:type schema:PropertyValue
    116 N1308d1a4fd404b5aaa691d3f5cd8d54a schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    117 schema:name Transcription Factors
    118 rdf:type schema:DefinedTerm
    119 N19558fd34bb5477389ee59cf8dce62ce schema:issueNumber 9
    120 rdf:type schema:PublicationIssue
    121 N1e6bd46f310f489fbb6ad778df0a27d8 rdf:first sg:person.01332124207.92
    122 rdf:rest N657dfea528e247749d727ac119b09ec4
    123 N351f4c3c06514035bb9a9adff5143cc7 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    124 schema:name Phosphorylation
    125 rdf:type schema:DefinedTerm
    126 N40ce1fd6d6ae485c8bb1810ad1c053a1 rdf:first sg:person.01173745301.12
    127 rdf:rest N9d76e8a974e44a228d0cff4b8119d7fd
    128 N4b8c87e0692f41f28aa0d2560c9615fa rdf:first sg:person.01276020470.05
    129 rdf:rest Ned4f9322df604910b39352c30b153c32
    130 N523e495158ca4cb6a5d343aaf415c869 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    131 schema:name Mutation
    132 rdf:type schema:DefinedTerm
    133 N63ac50719b27441e8dfcf00d8bb75ba3 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    134 schema:name STAT3 Transcription Factor
    135 rdf:type schema:DefinedTerm
    136 N657dfea528e247749d727ac119b09ec4 rdf:first sg:person.01023612122.13
    137 rdf:rest Nd3f6b305fe214018b7f0b905cb915a3f
    138 N69d52b507e90437f8911a7bc2d5d0e45 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    139 schema:name Interleukin-6
    140 rdf:type schema:DefinedTerm
    141 N701529e7ba40434e83ffbaeec9415dc4 rdf:first sg:person.01210116316.18
    142 rdf:rest Nf309fff505d44a9496ff4284db3e3a3a
    143 N7223f5dde4d54e49bce9d2bec6775fb5 schema:name Springer Nature - SN SciGraph project
    144 rdf:type schema:Organization
    145 N734087b0e25f45d4bd61d27a41f6b192 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    146 schema:name Proto-Oncogene Proteins B-raf
    147 rdf:type schema:DefinedTerm
    148 N75a8f6b8b78949fc8f7f3a4ed9c654ba schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    149 schema:name Melanocytes
    150 rdf:type schema:DefinedTerm
    151 N76c873945a92449787cf6b674c30ea19 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    152 schema:name Signal Transduction
    153 rdf:type schema:DefinedTerm
    154 N84e9bafe3048466facdeeca5eb410728 schema:name doi
    155 schema:value 10.1038/onc.2013.45
    156 rdf:type schema:PropertyValue
    157 N8b09df9aa37d4d32aba73a27a3d20c2e schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    158 schema:name Cell Survival
    159 rdf:type schema:DefinedTerm
    160 N8b74c47d560c47eaadb33f7224536551 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    161 schema:name Melanoma
    162 rdf:type schema:DefinedTerm
    163 N9d76e8a974e44a228d0cff4b8119d7fd rdf:first sg:person.0631770737.43
    164 rdf:rest N4b8c87e0692f41f28aa0d2560c9615fa
    165 Nac43bd5fc528469cb16edf4c0d6b315f rdf:first sg:person.01125632101.34
    166 rdf:rest N40ce1fd6d6ae485c8bb1810ad1c053a1
    167 Nadcdcacc3f3c4fa68ab4346a67c12d1f schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    168 schema:name Humans
    169 rdf:type schema:DefinedTerm
    170 Nb10b91e229f1400d833487e5d02f28a1 schema:name dimensions_id
    171 schema:value pub.1002813670
    172 rdf:type schema:PropertyValue
    173 Nbea66abd10234fda9bd19830ed79cc77 rdf:first sg:person.0654633307.36
    174 rdf:rest N701529e7ba40434e83ffbaeec9415dc4
    175 Ncea63fac66c34572847bb8e371b28078 schema:volumeNumber 33
    176 rdf:type schema:PublicationVolume
    177 Nd3f6b305fe214018b7f0b905cb915a3f rdf:first sg:person.01140040522.17
    178 rdf:rest Nac43bd5fc528469cb16edf4c0d6b315f
    179 Ned4f9322df604910b39352c30b153c32 rdf:first sg:person.013701550142.38
    180 rdf:rest Nbea66abd10234fda9bd19830ed79cc77
    181 Nf174469205c449bdbf8ab0373944fff6 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    182 schema:name Promoter Regions, Genetic
    183 rdf:type schema:DefinedTerm
    184 Nf309fff505d44a9496ff4284db3e3a3a rdf:first sg:person.01101732762.50
    185 rdf:rest rdf:nil
    186 Nf54c4a76f7674d78ac2378c0979f63a7 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    187 schema:name Myeloid Cell Leukemia Sequence 1 Protein
    188 rdf:type schema:DefinedTerm
    189 anzsrc-for:11 schema:inDefinedTermSet anzsrc-for:
    190 schema:name Medical and Health Sciences
    191 rdf:type schema:DefinedTerm
    192 anzsrc-for:1112 schema:inDefinedTermSet anzsrc-for:
    193 schema:name Oncology and Carcinogenesis
    194 rdf:type schema:DefinedTerm
    195 sg:grant.6713550 http://pending.schema.org/fundedItem sg:pub.10.1038/onc.2013.45
    196 rdf:type schema:MonetaryGrant
    197 sg:journal.1097543 schema:issn 0950-9232
    198 1476-5594
    199 schema:name Oncogene
    200 schema:publisher Springer Nature
    201 rdf:type schema:Periodical
    202 sg:person.01023612122.13 schema:affiliation grid-institutes:grid.413252.3
    203 schema:familyName Boyd
    204 schema:givenName S C
    205 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01023612122.13
    206 rdf:type schema:Person
    207 sg:person.01101732762.50 schema:affiliation grid-institutes:grid.413252.3
    208 schema:familyName Rizos
    209 schema:givenName H
    210 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01101732762.50
    211 rdf:type schema:Person
    212 sg:person.01125632101.34 schema:affiliation grid-institutes:grid.413252.3
    213 schema:familyName Gowrishankar
    214 schema:givenName K
    215 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01125632101.34
    216 rdf:type schema:Person
    217 sg:person.01140040522.17 schema:affiliation grid-institutes:grid.413252.3
    218 schema:familyName Mijatov
    219 schema:givenName B
    220 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01140040522.17
    221 rdf:type schema:Person
    222 sg:person.01173745301.12 schema:affiliation grid-institutes:grid.413252.3
    223 schema:familyName Snoyman
    224 schema:givenName S
    225 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01173745301.12
    226 rdf:type schema:Person
    227 sg:person.01210116316.18 schema:affiliation grid-institutes:grid.266842.c
    228 schema:familyName Zhang
    229 schema:givenName X D
    230 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01210116316.18
    231 rdf:type schema:Person
    232 sg:person.01276020470.05 schema:affiliation grid-institutes:grid.419690.3
    233 schema:familyName Scolyer
    234 schema:givenName R A
    235 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01276020470.05
    236 rdf:type schema:Person
    237 sg:person.01332124207.92 schema:affiliation grid-institutes:grid.413252.3
    238 schema:familyName Becker
    239 schema:givenName T M
    240 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01332124207.92
    241 rdf:type schema:Person
    242 sg:person.013701550142.38 schema:affiliation grid-institutes:grid.419690.3
    243 schema:familyName Mann
    244 schema:givenName G J
    245 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.013701550142.38
    246 rdf:type schema:Person
    247 sg:person.0631770737.43 schema:affiliation grid-institutes:grid.413252.3
    248 schema:familyName Pupo
    249 schema:givenName G M
    250 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0631770737.43
    251 rdf:type schema:Person
    252 sg:person.0654633307.36 schema:affiliation grid-institutes:grid.419690.3
    253 schema:familyName Kefford
    254 schema:givenName R F
    255 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0654633307.36
    256 rdf:type schema:Person
    257 sg:pub.10.1007/s00018-008-8637-6 schema:sameAs https://app.dimensions.ai/details/publication/pub.1023498818
    258 https://doi.org/10.1007/s00018-008-8637-6
    259 rdf:type schema:CreativeWork
    260 sg:pub.10.1007/s10555-005-1580-1 schema:sameAs https://app.dimensions.ai/details/publication/pub.1047575709
    261 https://doi.org/10.1007/s10555-005-1580-1
    262 rdf:type schema:CreativeWork
    263 sg:pub.10.1007/s11912-010-0095-2 schema:sameAs https://app.dimensions.ai/details/publication/pub.1003251632
    264 https://doi.org/10.1007/s11912-010-0095-2
    265 rdf:type schema:CreativeWork
    266 sg:pub.10.1038/cddis.2010.48 schema:sameAs https://app.dimensions.ai/details/publication/pub.1005879650
    267 https://doi.org/10.1038/cddis.2010.48
    268 rdf:type schema:CreativeWork
    269 sg:pub.10.1038/modpathol.3800750 schema:sameAs https://app.dimensions.ai/details/publication/pub.1022673157
    270 https://doi.org/10.1038/modpathol.3800750
    271 rdf:type schema:CreativeWork
    272 sg:pub.10.1038/nature03890 schema:sameAs https://app.dimensions.ai/details/publication/pub.1003324113
    273 https://doi.org/10.1038/nature03890
    274 rdf:type schema:CreativeWork
    275 sg:pub.10.1038/nrc1275 schema:sameAs https://app.dimensions.ai/details/publication/pub.1031068002
    276 https://doi.org/10.1038/nrc1275
    277 rdf:type schema:CreativeWork
    278 sg:pub.10.1038/nrm909 schema:sameAs https://app.dimensions.ai/details/publication/pub.1045111933
    279 https://doi.org/10.1038/nrm909
    280 rdf:type schema:CreativeWork
    281 sg:pub.10.1038/onc.2008.448 schema:sameAs https://app.dimensions.ai/details/publication/pub.1027217991
    282 https://doi.org/10.1038/onc.2008.448
    283 rdf:type schema:CreativeWork
    284 sg:pub.10.1038/sj.bjc.6604793 schema:sameAs https://app.dimensions.ai/details/publication/pub.1028780915
    285 https://doi.org/10.1038/sj.bjc.6604793
    286 rdf:type schema:CreativeWork
    287 sg:pub.10.1038/sj.bjc.6605691 schema:sameAs https://app.dimensions.ai/details/publication/pub.1012090202
    288 https://doi.org/10.1038/sj.bjc.6605691
    289 rdf:type schema:CreativeWork
    290 sg:pub.10.1038/sj.onc.1205859 schema:sameAs https://app.dimensions.ai/details/publication/pub.1014860210
    291 https://doi.org/10.1038/sj.onc.1205859
    292 rdf:type schema:CreativeWork
    293 sg:pub.10.1038/sj.onc.1209464 schema:sameAs https://app.dimensions.ai/details/publication/pub.1038055616
    294 https://doi.org/10.1038/sj.onc.1209464
    295 rdf:type schema:CreativeWork
    296 sg:pub.10.1186/1476-4598-9-165 schema:sameAs https://app.dimensions.ai/details/publication/pub.1048943178
    297 https://doi.org/10.1186/1476-4598-9-165
    298 rdf:type schema:CreativeWork
    299 sg:pub.10.1186/1476-4598-9-217 schema:sameAs https://app.dimensions.ai/details/publication/pub.1052907373
    300 https://doi.org/10.1186/1476-4598-9-217
    301 rdf:type schema:CreativeWork
    302 grid-institutes:grid.266842.c schema:alternateName Immunology and Oncology Unit, University of Newcastle, Newcastle, New South Wales, Australia
    303 schema:name Immunology and Oncology Unit, University of Newcastle, Newcastle, New South Wales, Australia
    304 rdf:type schema:Organization
    305 grid-institutes:grid.413252.3 schema:alternateName Westmead Institute for Cancer Research, University of Sydney at Westmead Millennium Institute, Westmead Hospital, Sydney, New South Wales, Australia
    306 schema:name Westmead Institute for Cancer Research, University of Sydney at Westmead Millennium Institute, Westmead Hospital, Sydney, New South Wales, Australia
    307 rdf:type schema:Organization
    308 grid-institutes:grid.419690.3 schema:alternateName Melanoma Institute Australia, Sydney, New South Wales, Australia
    309 schema:name Melanoma Institute Australia, Sydney, New South Wales, Australia
    310 Westmead Institute for Cancer Research, University of Sydney at Westmead Millennium Institute, Westmead Hospital, Sydney, New South Wales, Australia
    311 rdf:type schema:Organization
     




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


    ...