MEK5/ERK5 activation regulates colon cancer stem-like cell properties View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2019-12

AUTHORS

Diane M. Pereira, Sofia. E. Gomes, Pedro M. Borralho, Cecília M. P. Rodrigues

ABSTRACT

Colon cancer has been proposed to be sustained by a small subpopulation of stem-like cells with unique properties allowing them to survive conventional therapies and drive tumor recurrence. Identification of targetable signaling pathways contributing to malignant stem-like cell maintenance may therefore translate into new therapeutic strategies to overcome drug resistance. Here we demonstrated that MEK5/ERK5 signaling activation is associated with stem-like malignant phenotypes. Conversely, using a panel of cell line-derived three-dimensional models, we showed that ERK5 inhibition markedly suppresses the molecular and functional features of colon cancer stem-like cells. Particularly, pharmacological inhibition of ERK5 using XMD8-92 reduced the rate of primary and secondary sphere formation, the expression of pluripotency transcription factors SOX2, NANOG, and OCT4, and the proportion of tumor cells with increased ALDH activity. Notably, this was further associated with increased sensitivity to 5-fluorouracil-based chemotherapy. Mechanistically, ERK5 inhibition resulted in decreased IL-8 expression and NF-κB transcriptional activity, suggesting a possible ERK5/NF-κB/IL-8 signaling axis regulating stem-like cell malignancy. Taken together, our results provide proof of principle that ERK5-targeted inhibition may be a promising therapeutic approach to eliminate drug-resistant cancer stem-like cells and improve colon cancer treatment. More... »

PAGES

68

References to SciGraph publications

  • 2016-12. MEK5 overexpression is associated with the occurrence and development of colorectal cancer in BMC CANCER
  • 2012-12. Subtypes of primary colorectal tumors correlate with response to targeted treatment in colorectal cell lines in BMC MEDICAL GENOMICS
  • 2007-01. Identification and expansion of human colon-cancer-initiating cells in NATURE
  • 2016-05-17. ERK5 signalling rescues intestinal epithelial turnover and tumour cell proliferation upon ERK1/2 abrogation in NATURE COMMUNICATIONS
  • 2018-08. A kinome-wide high-content siRNA screen identifies MEK5–ERK5 signaling as critical for breast cancer cell EMT and metastasis in ONCOGENE
  • 2012-12. Expression of the phosphorylated MEK5 protein is associated with TNM staging of colorectal cancer in BMC CANCER
  • 2007-01. A human colon cancer cell capable of initiating tumour growth in immunodeficient mice in NATURE
  • 2014-07. Decreased mitochondrial priming determines chemoresistance of colon cancer stem cells in CELL DEATH & DIFFERENTIATION
  • 2011-09. Tumour-initiating stem-like cells in human prostate cancer exhibit increased NF-κB signalling in NATURE COMMUNICATIONS
  • 2003-12. Knockout of ERK5 causes multiple defects in placental and embryonic development in BMC DEVELOPMENTAL BIOLOGY
  • 1994-08. Serum levels of cytokines in patients with colorectal cancer: Possible involvement of interleukin-6 and interleukin-8 in hematogenous metastasis in JOURNAL OF GASTROENTEROLOGY
  • 2003-03. MEK5 overexpression is associated with metastatic prostate cancer, and stimulates proliferation, MMP-9 expression and invasion in ONCOGENE
  • 2017-04-11. EMT, CSCs, and drug resistance: the mechanistic link and clinical implications in NATURE REVIEWS CLINICAL ONCOLOGY
  • 2010-04. Expansion of CD133+ colon cancer cultures retaining stem cell properties to enable cancer stem cell target discovery in BRITISH JOURNAL OF CANCER
  • 2009-05. Role of BCRP as a biomarker for predicting resistance to 5-fluorouracil in breast cancer in CANCER CHEMOTHERAPY AND PHARMACOLOGY
  • 2010-12. The Wnt/β-catenin pathway regulates growth and maintenance of colonospheres in MOLECULAR CANCER
  • 2015-04. Aberrant MEK5/ERK5 signalling contributes to human colon cancer progression via NF-κB activation in CELL DEATH & DISEASE
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/s41420-019-0150-1

    DOI

    http://dx.doi.org/10.1038/s41420-019-0150-1

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1112057447

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/30774996


    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/2008/1112", 
            "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
            "name": "Oncology and Carcinogenesis", 
            "type": "DefinedTerm"
          }, 
          {
            "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"
          }
        ], 
        "author": [
          {
            "affiliation": {
              "alternateName": "University of Lisbon", 
              "id": "https://www.grid.ac/institutes/grid.9983.b", 
              "name": [
                "Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Lisbon, Portugal"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Pereira", 
            "givenName": "Diane M.", 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "University of Lisbon", 
              "id": "https://www.grid.ac/institutes/grid.9983.b", 
              "name": [
                "Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Lisbon, Portugal"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Gomes", 
            "givenName": "Sofia. E.", 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "University of Lisbon", 
              "id": "https://www.grid.ac/institutes/grid.9983.b", 
              "name": [
                "Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Lisbon, Portugal"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Borralho", 
            "givenName": "Pedro M.", 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "University of Lisbon", 
              "id": "https://www.grid.ac/institutes/grid.9983.b", 
              "name": [
                "Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Lisbon, Portugal"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Rodrigues", 
            "givenName": "Cec\u00edlia M. P.", 
            "type": "Person"
          }
        ], 
        "citation": [
          {
            "id": "https://doi.org/10.1016/j.ccr.2010.08.008", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1001630944"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/cdd.2014.37", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1001682760", 
              "https://doi.org/10.1038/cdd.2014.37"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1186/1476-4598-9-212", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1002613769", 
              "https://doi.org/10.1186/1476-4598-9-212"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nature05372", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1002972347", 
              "https://doi.org/10.1038/nature05372"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nature05372", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1002972347", 
              "https://doi.org/10.1038/nature05372"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1073/pnas.0603373103", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1003627930"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/j.stem.2011.04.007", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1004500965"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/j.yexcr.2014.10.003", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1005488875"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/j.stem.2011.10.008", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1005993914"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1159/000085964", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1006357405"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1159/000085964", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1006357405"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1056/nejmoa1506597", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1008184382"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1073/pnas.89.5.1875", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1008212871"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1186/1471-213x-3-11", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1008372752", 
              "https://doi.org/10.1186/1471-213x-3-11"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/j.canlet.2014.05.011", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1008932835"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1002/ijc.25562", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1009834454"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1371/journal.pone.0002428", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1010141743"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1038/emboj.2008.114", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1010198834"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/j.stem.2011.02.020", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1010215023"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1182/blood-2009-04-217042", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1010448675"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1158/0008-5472.can-06-3126", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1010617336"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1073/pnas.142293999", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1010624940"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1158/0008-5472.can-10-0732", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1012806954"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/j.cellsig.2012.07.007", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1015705492"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/ncomms11551", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1015819509", 
              "https://doi.org/10.1038/ncomms11551"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1073/pnas.1609019113", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1016062429"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/j.devcel.2010.12.005", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1018621115"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1093/embo-reports/kve177", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1019651123"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.18632/oncotarget.5337", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1020530123"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1007/bf02361238", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1021504114", 
              "https://doi.org/10.1007/bf02361238"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1007/bf02361238", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1021504114", 
              "https://doi.org/10.1007/bf02361238"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1007/s00280-008-0838-z", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1021847997", 
              "https://doi.org/10.1007/s00280-008-0838-z"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1007/s00280-008-0838-z", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1021847997", 
              "https://doi.org/10.1007/s00280-008-0838-z"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/j.celrep.2016.07.033", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1021918737"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1074/jbc.m113.477950", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1024286425"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1186/s12885-016-2327-9", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1025902266", 
              "https://doi.org/10.1186/s12885-016-2327-9"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1111/brv.12293", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1025990254"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/ncomms1159", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1026349910", 
              "https://doi.org/10.1038/ncomms1159"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nature05384", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1026901039", 
              "https://doi.org/10.1038/nature05384"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nature05384", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1026901039", 
              "https://doi.org/10.1038/nature05384"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/sj.onc.1206154", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1029773545", 
              "https://doi.org/10.1038/sj.onc.1206154"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/sj.onc.1206154", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1029773545", 
              "https://doi.org/10.1038/sj.onc.1206154"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/j.stem.2014.11.012", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1030378975"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1074/jbc.m207573200", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1031827374"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1523/jneurosci.3745-14.2015", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1032506018"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1523/jneurosci.3324-13.2014", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1032920419"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1074/jbc.m410994200", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1034431301"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/j.bbagen.2012.11.008", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1034491366"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/j.celrep.2015.09.016", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1035856598"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/cddis.2015.83", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1037019618", 
              "https://doi.org/10.1038/cddis.2015.83"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1371/journal.pone.0061948", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1038032957"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/j.yexcr.2004.05.033", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1039058981"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1128/mcb.25.1.336-345.2005", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1039090002"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/sj.bjc.6605610", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1039481747", 
              "https://doi.org/10.1038/sj.bjc.6605610"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/sj.bjc.6605610", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1039481747", 
              "https://doi.org/10.1038/sj.bjc.6605610"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1158/1541-7786.mcr-14-0604", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1039577003"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/j.drudis.2016.06.010", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1039818373"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1158/0008-5472.can-11-0221", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1040716811"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1158/0008-5472.can-14-0013", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1041620473"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1073/pnas.0703478104", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1041933940"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1186/1755-8794-5-66", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1042233177", 
              "https://doi.org/10.1186/1755-8794-5-66"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1093/carcin/bgn164", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1042640094"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1186/1471-2407-12-127", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1042877278", 
              "https://doi.org/10.1186/1471-2407-12-127"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/j.stem.2009.05.019", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1042983803"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/j.neo.2014.12.004", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1043235824"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/j.stem.2007.08.001", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1043575176"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.18632/oncotarget.9107", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1046445029"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1002/stem.741", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1047088831"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1006/cyto.1999.0518", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1047729139"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/j.cell.2009.08.017", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1049506378"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1158/0008-5472.can-08-4418", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1051237515"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1053/j.gastro.2011.04.008", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1051659712"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.3390/ijms140510143", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1051934526"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1158/1078-0432.ccr-10-2743", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1053110288"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1126/science.274.5288.787", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1062554673"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1126/scisignal.aaa3206", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1062685422"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1158/0008-5472.can-14-2430", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1063215741"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.3892/ol.2016.4937", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1071527696"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1002/jlb.56.5.554", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1082398715"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nrclinonc.2017.44", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1084764660", 
              "https://doi.org/10.1038/nrclinonc.2017.44"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/j.jmb.2017.04.013", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1085117544"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.18632/oncotarget.23305", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1099685649"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1073/pnas.1707929115", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1101340662"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/s41388-018-0270-8", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1103690075", 
              "https://doi.org/10.1038/s41388-018-0270-8"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/s41388-018-0270-8", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1103690075", 
              "https://doi.org/10.1038/s41388-018-0270-8"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.3389/fonc.2018.00166", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1104037395"
            ], 
            "type": "CreativeWork"
          }
        ], 
        "datePublished": "2019-12", 
        "datePublishedReg": "2019-12-01", 
        "description": "Colon cancer has been proposed to be sustained by a small subpopulation of stem-like cells with unique properties allowing them to survive conventional therapies and drive tumor recurrence. Identification of targetable signaling pathways contributing to malignant stem-like cell maintenance may therefore translate into new therapeutic strategies to overcome drug resistance. Here we demonstrated that MEK5/ERK5 signaling activation is associated with stem-like malignant phenotypes. Conversely, using a panel of cell line-derived three-dimensional models, we showed that ERK5 inhibition markedly suppresses the molecular and functional features of colon cancer stem-like cells. Particularly, pharmacological inhibition of ERK5 using XMD8-92 reduced the rate of primary and secondary sphere formation, the expression of pluripotency transcription factors SOX2, NANOG, and OCT4, and the proportion of tumor cells with increased ALDH activity. Notably, this was further associated with increased sensitivity to 5-fluorouracil-based chemotherapy. Mechanistically, ERK5 inhibition resulted in decreased IL-8 expression and NF-\u03baB transcriptional activity, suggesting a possible ERK5/NF-\u03baB/IL-8 signaling axis regulating stem-like cell malignancy. Taken together, our results provide proof of principle that ERK5-targeted inhibition may be a promising therapeutic approach to eliminate drug-resistant cancer stem-like cells and improve colon cancer treatment.", 
        "genre": "research_article", 
        "id": "sg:pub.10.1038/s41420-019-0150-1", 
        "inLanguage": [
          "en"
        ], 
        "isAccessibleForFree": false, 
        "isPartOf": [
          {
            "id": "sg:journal.1052270", 
            "issn": [
              "2058-7716"
            ], 
            "name": "Cell Death Discovery", 
            "type": "Periodical"
          }, 
          {
            "issueNumber": "1", 
            "type": "PublicationIssue"
          }, 
          {
            "type": "PublicationVolume", 
            "volumeNumber": "5"
          }
        ], 
        "name": "MEK5/ERK5 activation regulates colon cancer stem-like cell properties", 
        "pagination": "68", 
        "productId": [
          {
            "name": "readcube_id", 
            "type": "PropertyValue", 
            "value": [
              "398053bebb6006be4e4fcfda2b20ca8e09794db1b0ddbc5bbcf446e78dee5a7c"
            ]
          }, 
          {
            "name": "pubmed_id", 
            "type": "PropertyValue", 
            "value": [
              "30774996"
            ]
          }, 
          {
            "name": "nlm_unique_id", 
            "type": "PropertyValue", 
            "value": [
              "101665035"
            ]
          }, 
          {
            "name": "doi", 
            "type": "PropertyValue", 
            "value": [
              "10.1038/s41420-019-0150-1"
            ]
          }, 
          {
            "name": "dimensions_id", 
            "type": "PropertyValue", 
            "value": [
              "pub.1112057447"
            ]
          }
        ], 
        "sameAs": [
          "https://doi.org/10.1038/s41420-019-0150-1", 
          "https://app.dimensions.ai/details/publication/pub.1112057447"
        ], 
        "sdDataset": "articles", 
        "sdDatePublished": "2019-04-11T09:13", 
        "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/v90/0000000338_0000000338/records_47989_00000002.jsonl", 
        "type": "ScholarlyArticle", 
        "url": "https://www.nature.com/articles/s41420-019-0150-1"
      }
    ]
     

    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/s41420-019-0150-1'

    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/s41420-019-0150-1'

    Turtle is a human-readable linked data format.

    curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1038/s41420-019-0150-1'

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

    curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1038/s41420-019-0150-1'


     

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

    336 TRIPLES      21 PREDICATES      107 URIs      21 LITERALS      9 BLANK NODES

    Subject Predicate Object
    1 sg:pub.10.1038/s41420-019-0150-1 schema:about anzsrc-for:11
    2 anzsrc-for:1112
    3 schema:author Nc0679cd6a0354dce9117891c195e89ad
    4 schema:citation sg:pub.10.1007/bf02361238
    5 sg:pub.10.1007/s00280-008-0838-z
    6 sg:pub.10.1038/cdd.2014.37
    7 sg:pub.10.1038/cddis.2015.83
    8 sg:pub.10.1038/nature05372
    9 sg:pub.10.1038/nature05384
    10 sg:pub.10.1038/ncomms11551
    11 sg:pub.10.1038/ncomms1159
    12 sg:pub.10.1038/nrclinonc.2017.44
    13 sg:pub.10.1038/s41388-018-0270-8
    14 sg:pub.10.1038/sj.bjc.6605610
    15 sg:pub.10.1038/sj.onc.1206154
    16 sg:pub.10.1186/1471-213x-3-11
    17 sg:pub.10.1186/1471-2407-12-127
    18 sg:pub.10.1186/1476-4598-9-212
    19 sg:pub.10.1186/1755-8794-5-66
    20 sg:pub.10.1186/s12885-016-2327-9
    21 https://doi.org/10.1002/ijc.25562
    22 https://doi.org/10.1002/jlb.56.5.554
    23 https://doi.org/10.1002/stem.741
    24 https://doi.org/10.1006/cyto.1999.0518
    25 https://doi.org/10.1016/j.bbagen.2012.11.008
    26 https://doi.org/10.1016/j.canlet.2014.05.011
    27 https://doi.org/10.1016/j.ccr.2010.08.008
    28 https://doi.org/10.1016/j.cell.2009.08.017
    29 https://doi.org/10.1016/j.cellsig.2012.07.007
    30 https://doi.org/10.1016/j.celrep.2015.09.016
    31 https://doi.org/10.1016/j.celrep.2016.07.033
    32 https://doi.org/10.1016/j.devcel.2010.12.005
    33 https://doi.org/10.1016/j.drudis.2016.06.010
    34 https://doi.org/10.1016/j.jmb.2017.04.013
    35 https://doi.org/10.1016/j.neo.2014.12.004
    36 https://doi.org/10.1016/j.stem.2007.08.001
    37 https://doi.org/10.1016/j.stem.2009.05.019
    38 https://doi.org/10.1016/j.stem.2011.02.020
    39 https://doi.org/10.1016/j.stem.2011.04.007
    40 https://doi.org/10.1016/j.stem.2011.10.008
    41 https://doi.org/10.1016/j.stem.2014.11.012
    42 https://doi.org/10.1016/j.yexcr.2004.05.033
    43 https://doi.org/10.1016/j.yexcr.2014.10.003
    44 https://doi.org/10.1038/emboj.2008.114
    45 https://doi.org/10.1053/j.gastro.2011.04.008
    46 https://doi.org/10.1056/nejmoa1506597
    47 https://doi.org/10.1073/pnas.0603373103
    48 https://doi.org/10.1073/pnas.0703478104
    49 https://doi.org/10.1073/pnas.142293999
    50 https://doi.org/10.1073/pnas.1609019113
    51 https://doi.org/10.1073/pnas.1707929115
    52 https://doi.org/10.1073/pnas.89.5.1875
    53 https://doi.org/10.1074/jbc.m113.477950
    54 https://doi.org/10.1074/jbc.m207573200
    55 https://doi.org/10.1074/jbc.m410994200
    56 https://doi.org/10.1093/carcin/bgn164
    57 https://doi.org/10.1093/embo-reports/kve177
    58 https://doi.org/10.1111/brv.12293
    59 https://doi.org/10.1126/science.274.5288.787
    60 https://doi.org/10.1126/scisignal.aaa3206
    61 https://doi.org/10.1128/mcb.25.1.336-345.2005
    62 https://doi.org/10.1158/0008-5472.can-06-3126
    63 https://doi.org/10.1158/0008-5472.can-08-4418
    64 https://doi.org/10.1158/0008-5472.can-10-0732
    65 https://doi.org/10.1158/0008-5472.can-11-0221
    66 https://doi.org/10.1158/0008-5472.can-14-0013
    67 https://doi.org/10.1158/0008-5472.can-14-2430
    68 https://doi.org/10.1158/1078-0432.ccr-10-2743
    69 https://doi.org/10.1158/1541-7786.mcr-14-0604
    70 https://doi.org/10.1159/000085964
    71 https://doi.org/10.1182/blood-2009-04-217042
    72 https://doi.org/10.1371/journal.pone.0002428
    73 https://doi.org/10.1371/journal.pone.0061948
    74 https://doi.org/10.1523/jneurosci.3324-13.2014
    75 https://doi.org/10.1523/jneurosci.3745-14.2015
    76 https://doi.org/10.18632/oncotarget.23305
    77 https://doi.org/10.18632/oncotarget.5337
    78 https://doi.org/10.18632/oncotarget.9107
    79 https://doi.org/10.3389/fonc.2018.00166
    80 https://doi.org/10.3390/ijms140510143
    81 https://doi.org/10.3892/ol.2016.4937
    82 schema:datePublished 2019-12
    83 schema:datePublishedReg 2019-12-01
    84 schema:description Colon cancer has been proposed to be sustained by a small subpopulation of stem-like cells with unique properties allowing them to survive conventional therapies and drive tumor recurrence. Identification of targetable signaling pathways contributing to malignant stem-like cell maintenance may therefore translate into new therapeutic strategies to overcome drug resistance. Here we demonstrated that MEK5/ERK5 signaling activation is associated with stem-like malignant phenotypes. Conversely, using a panel of cell line-derived three-dimensional models, we showed that ERK5 inhibition markedly suppresses the molecular and functional features of colon cancer stem-like cells. Particularly, pharmacological inhibition of ERK5 using XMD8-92 reduced the rate of primary and secondary sphere formation, the expression of pluripotency transcription factors SOX2, NANOG, and OCT4, and the proportion of tumor cells with increased ALDH activity. Notably, this was further associated with increased sensitivity to 5-fluorouracil-based chemotherapy. Mechanistically, ERK5 inhibition resulted in decreased <i>IL-8</i> expression and NF-κB transcriptional activity, suggesting a possible ERK5/NF-κB/IL-8 signaling axis regulating stem-like cell malignancy. Taken together, our results provide proof of principle that ERK5-targeted inhibition may be a promising therapeutic approach to eliminate drug-resistant cancer stem-like cells and improve colon cancer treatment.
    85 schema:genre research_article
    86 schema:inLanguage en
    87 schema:isAccessibleForFree false
    88 schema:isPartOf Nbca4d27515ad4a0cadf873a31dc9aa23
    89 Nd2bc9ec262bc4277939a61192f5063f6
    90 sg:journal.1052270
    91 schema:name MEK5/ERK5 activation regulates colon cancer stem-like cell properties
    92 schema:pagination 68
    93 schema:productId N0057c6ada5294cabb78dc7c9f656e4a3
    94 N25fa05579b8b40f09550ee211f4e837f
    95 N550dc81630a043c28d0eaa67c81b0dde
    96 N6feeefa498404e15b81f184f8b43b9eb
    97 N939a9d70969544b59da2af8fa67e6449
    98 schema:sameAs https://app.dimensions.ai/details/publication/pub.1112057447
    99 https://doi.org/10.1038/s41420-019-0150-1
    100 schema:sdDatePublished 2019-04-11T09:13
    101 schema:sdLicense https://scigraph.springernature.com/explorer/license/
    102 schema:sdPublisher N57af14318e8a41f5979d1aa4bd56df8d
    103 schema:url https://www.nature.com/articles/s41420-019-0150-1
    104 sgo:license sg:explorer/license/
    105 sgo:sdDataset articles
    106 rdf:type schema:ScholarlyArticle
    107 N0057c6ada5294cabb78dc7c9f656e4a3 schema:name pubmed_id
    108 schema:value 30774996
    109 rdf:type schema:PropertyValue
    110 N25fa05579b8b40f09550ee211f4e837f schema:name dimensions_id
    111 schema:value pub.1112057447
    112 rdf:type schema:PropertyValue
    113 N550dc81630a043c28d0eaa67c81b0dde schema:name doi
    114 schema:value 10.1038/s41420-019-0150-1
    115 rdf:type schema:PropertyValue
    116 N57af14318e8a41f5979d1aa4bd56df8d schema:name Springer Nature - SN SciGraph project
    117 rdf:type schema:Organization
    118 N615efea4b5ac43ad985f2b130b771b42 schema:affiliation https://www.grid.ac/institutes/grid.9983.b
    119 schema:familyName Pereira
    120 schema:givenName Diane M.
    121 rdf:type schema:Person
    122 N6feeefa498404e15b81f184f8b43b9eb schema:name nlm_unique_id
    123 schema:value 101665035
    124 rdf:type schema:PropertyValue
    125 N939a9d70969544b59da2af8fa67e6449 schema:name readcube_id
    126 schema:value 398053bebb6006be4e4fcfda2b20ca8e09794db1b0ddbc5bbcf446e78dee5a7c
    127 rdf:type schema:PropertyValue
    128 N9f760fe76421456bace025084895ee7c schema:affiliation https://www.grid.ac/institutes/grid.9983.b
    129 schema:familyName Borralho
    130 schema:givenName Pedro M.
    131 rdf:type schema:Person
    132 Na0cc5e2e16774e6786b758925ea3ca09 rdf:first Nd3e8dc24112d499b888778d1bf8d6a68
    133 rdf:rest Na54fc504501c438bbbdebb6bfaa2f382
    134 Na54fc504501c438bbbdebb6bfaa2f382 rdf:first N9f760fe76421456bace025084895ee7c
    135 rdf:rest Ndbb8a008f4ac4b9a981f1c1039cb0816
    136 Nbca4d27515ad4a0cadf873a31dc9aa23 schema:issueNumber 1
    137 rdf:type schema:PublicationIssue
    138 Nc0679cd6a0354dce9117891c195e89ad rdf:first N615efea4b5ac43ad985f2b130b771b42
    139 rdf:rest Na0cc5e2e16774e6786b758925ea3ca09
    140 Nd2bc9ec262bc4277939a61192f5063f6 schema:volumeNumber 5
    141 rdf:type schema:PublicationVolume
    142 Nd3e8dc24112d499b888778d1bf8d6a68 schema:affiliation https://www.grid.ac/institutes/grid.9983.b
    143 schema:familyName Gomes
    144 schema:givenName Sofia. E.
    145 rdf:type schema:Person
    146 Ndbb8a008f4ac4b9a981f1c1039cb0816 rdf:first Nfb8e6a69b24a4859be80f105f32df486
    147 rdf:rest rdf:nil
    148 Nfb8e6a69b24a4859be80f105f32df486 schema:affiliation https://www.grid.ac/institutes/grid.9983.b
    149 schema:familyName Rodrigues
    150 schema:givenName Cecília M. P.
    151 rdf:type schema:Person
    152 anzsrc-for:11 schema:inDefinedTermSet anzsrc-for:
    153 schema:name Medical and Health Sciences
    154 rdf:type schema:DefinedTerm
    155 anzsrc-for:1112 schema:inDefinedTermSet anzsrc-for:
    156 schema:name Oncology and Carcinogenesis
    157 rdf:type schema:DefinedTerm
    158 sg:journal.1052270 schema:issn 2058-7716
    159 schema:name Cell Death Discovery
    160 rdf:type schema:Periodical
    161 sg:pub.10.1007/bf02361238 schema:sameAs https://app.dimensions.ai/details/publication/pub.1021504114
    162 https://doi.org/10.1007/bf02361238
    163 rdf:type schema:CreativeWork
    164 sg:pub.10.1007/s00280-008-0838-z schema:sameAs https://app.dimensions.ai/details/publication/pub.1021847997
    165 https://doi.org/10.1007/s00280-008-0838-z
    166 rdf:type schema:CreativeWork
    167 sg:pub.10.1038/cdd.2014.37 schema:sameAs https://app.dimensions.ai/details/publication/pub.1001682760
    168 https://doi.org/10.1038/cdd.2014.37
    169 rdf:type schema:CreativeWork
    170 sg:pub.10.1038/cddis.2015.83 schema:sameAs https://app.dimensions.ai/details/publication/pub.1037019618
    171 https://doi.org/10.1038/cddis.2015.83
    172 rdf:type schema:CreativeWork
    173 sg:pub.10.1038/nature05372 schema:sameAs https://app.dimensions.ai/details/publication/pub.1002972347
    174 https://doi.org/10.1038/nature05372
    175 rdf:type schema:CreativeWork
    176 sg:pub.10.1038/nature05384 schema:sameAs https://app.dimensions.ai/details/publication/pub.1026901039
    177 https://doi.org/10.1038/nature05384
    178 rdf:type schema:CreativeWork
    179 sg:pub.10.1038/ncomms11551 schema:sameAs https://app.dimensions.ai/details/publication/pub.1015819509
    180 https://doi.org/10.1038/ncomms11551
    181 rdf:type schema:CreativeWork
    182 sg:pub.10.1038/ncomms1159 schema:sameAs https://app.dimensions.ai/details/publication/pub.1026349910
    183 https://doi.org/10.1038/ncomms1159
    184 rdf:type schema:CreativeWork
    185 sg:pub.10.1038/nrclinonc.2017.44 schema:sameAs https://app.dimensions.ai/details/publication/pub.1084764660
    186 https://doi.org/10.1038/nrclinonc.2017.44
    187 rdf:type schema:CreativeWork
    188 sg:pub.10.1038/s41388-018-0270-8 schema:sameAs https://app.dimensions.ai/details/publication/pub.1103690075
    189 https://doi.org/10.1038/s41388-018-0270-8
    190 rdf:type schema:CreativeWork
    191 sg:pub.10.1038/sj.bjc.6605610 schema:sameAs https://app.dimensions.ai/details/publication/pub.1039481747
    192 https://doi.org/10.1038/sj.bjc.6605610
    193 rdf:type schema:CreativeWork
    194 sg:pub.10.1038/sj.onc.1206154 schema:sameAs https://app.dimensions.ai/details/publication/pub.1029773545
    195 https://doi.org/10.1038/sj.onc.1206154
    196 rdf:type schema:CreativeWork
    197 sg:pub.10.1186/1471-213x-3-11 schema:sameAs https://app.dimensions.ai/details/publication/pub.1008372752
    198 https://doi.org/10.1186/1471-213x-3-11
    199 rdf:type schema:CreativeWork
    200 sg:pub.10.1186/1471-2407-12-127 schema:sameAs https://app.dimensions.ai/details/publication/pub.1042877278
    201 https://doi.org/10.1186/1471-2407-12-127
    202 rdf:type schema:CreativeWork
    203 sg:pub.10.1186/1476-4598-9-212 schema:sameAs https://app.dimensions.ai/details/publication/pub.1002613769
    204 https://doi.org/10.1186/1476-4598-9-212
    205 rdf:type schema:CreativeWork
    206 sg:pub.10.1186/1755-8794-5-66 schema:sameAs https://app.dimensions.ai/details/publication/pub.1042233177
    207 https://doi.org/10.1186/1755-8794-5-66
    208 rdf:type schema:CreativeWork
    209 sg:pub.10.1186/s12885-016-2327-9 schema:sameAs https://app.dimensions.ai/details/publication/pub.1025902266
    210 https://doi.org/10.1186/s12885-016-2327-9
    211 rdf:type schema:CreativeWork
    212 https://doi.org/10.1002/ijc.25562 schema:sameAs https://app.dimensions.ai/details/publication/pub.1009834454
    213 rdf:type schema:CreativeWork
    214 https://doi.org/10.1002/jlb.56.5.554 schema:sameAs https://app.dimensions.ai/details/publication/pub.1082398715
    215 rdf:type schema:CreativeWork
    216 https://doi.org/10.1002/stem.741 schema:sameAs https://app.dimensions.ai/details/publication/pub.1047088831
    217 rdf:type schema:CreativeWork
    218 https://doi.org/10.1006/cyto.1999.0518 schema:sameAs https://app.dimensions.ai/details/publication/pub.1047729139
    219 rdf:type schema:CreativeWork
    220 https://doi.org/10.1016/j.bbagen.2012.11.008 schema:sameAs https://app.dimensions.ai/details/publication/pub.1034491366
    221 rdf:type schema:CreativeWork
    222 https://doi.org/10.1016/j.canlet.2014.05.011 schema:sameAs https://app.dimensions.ai/details/publication/pub.1008932835
    223 rdf:type schema:CreativeWork
    224 https://doi.org/10.1016/j.ccr.2010.08.008 schema:sameAs https://app.dimensions.ai/details/publication/pub.1001630944
    225 rdf:type schema:CreativeWork
    226 https://doi.org/10.1016/j.cell.2009.08.017 schema:sameAs https://app.dimensions.ai/details/publication/pub.1049506378
    227 rdf:type schema:CreativeWork
    228 https://doi.org/10.1016/j.cellsig.2012.07.007 schema:sameAs https://app.dimensions.ai/details/publication/pub.1015705492
    229 rdf:type schema:CreativeWork
    230 https://doi.org/10.1016/j.celrep.2015.09.016 schema:sameAs https://app.dimensions.ai/details/publication/pub.1035856598
    231 rdf:type schema:CreativeWork
    232 https://doi.org/10.1016/j.celrep.2016.07.033 schema:sameAs https://app.dimensions.ai/details/publication/pub.1021918737
    233 rdf:type schema:CreativeWork
    234 https://doi.org/10.1016/j.devcel.2010.12.005 schema:sameAs https://app.dimensions.ai/details/publication/pub.1018621115
    235 rdf:type schema:CreativeWork
    236 https://doi.org/10.1016/j.drudis.2016.06.010 schema:sameAs https://app.dimensions.ai/details/publication/pub.1039818373
    237 rdf:type schema:CreativeWork
    238 https://doi.org/10.1016/j.jmb.2017.04.013 schema:sameAs https://app.dimensions.ai/details/publication/pub.1085117544
    239 rdf:type schema:CreativeWork
    240 https://doi.org/10.1016/j.neo.2014.12.004 schema:sameAs https://app.dimensions.ai/details/publication/pub.1043235824
    241 rdf:type schema:CreativeWork
    242 https://doi.org/10.1016/j.stem.2007.08.001 schema:sameAs https://app.dimensions.ai/details/publication/pub.1043575176
    243 rdf:type schema:CreativeWork
    244 https://doi.org/10.1016/j.stem.2009.05.019 schema:sameAs https://app.dimensions.ai/details/publication/pub.1042983803
    245 rdf:type schema:CreativeWork
    246 https://doi.org/10.1016/j.stem.2011.02.020 schema:sameAs https://app.dimensions.ai/details/publication/pub.1010215023
    247 rdf:type schema:CreativeWork
    248 https://doi.org/10.1016/j.stem.2011.04.007 schema:sameAs https://app.dimensions.ai/details/publication/pub.1004500965
    249 rdf:type schema:CreativeWork
    250 https://doi.org/10.1016/j.stem.2011.10.008 schema:sameAs https://app.dimensions.ai/details/publication/pub.1005993914
    251 rdf:type schema:CreativeWork
    252 https://doi.org/10.1016/j.stem.2014.11.012 schema:sameAs https://app.dimensions.ai/details/publication/pub.1030378975
    253 rdf:type schema:CreativeWork
    254 https://doi.org/10.1016/j.yexcr.2004.05.033 schema:sameAs https://app.dimensions.ai/details/publication/pub.1039058981
    255 rdf:type schema:CreativeWork
    256 https://doi.org/10.1016/j.yexcr.2014.10.003 schema:sameAs https://app.dimensions.ai/details/publication/pub.1005488875
    257 rdf:type schema:CreativeWork
    258 https://doi.org/10.1038/emboj.2008.114 schema:sameAs https://app.dimensions.ai/details/publication/pub.1010198834
    259 rdf:type schema:CreativeWork
    260 https://doi.org/10.1053/j.gastro.2011.04.008 schema:sameAs https://app.dimensions.ai/details/publication/pub.1051659712
    261 rdf:type schema:CreativeWork
    262 https://doi.org/10.1056/nejmoa1506597 schema:sameAs https://app.dimensions.ai/details/publication/pub.1008184382
    263 rdf:type schema:CreativeWork
    264 https://doi.org/10.1073/pnas.0603373103 schema:sameAs https://app.dimensions.ai/details/publication/pub.1003627930
    265 rdf:type schema:CreativeWork
    266 https://doi.org/10.1073/pnas.0703478104 schema:sameAs https://app.dimensions.ai/details/publication/pub.1041933940
    267 rdf:type schema:CreativeWork
    268 https://doi.org/10.1073/pnas.142293999 schema:sameAs https://app.dimensions.ai/details/publication/pub.1010624940
    269 rdf:type schema:CreativeWork
    270 https://doi.org/10.1073/pnas.1609019113 schema:sameAs https://app.dimensions.ai/details/publication/pub.1016062429
    271 rdf:type schema:CreativeWork
    272 https://doi.org/10.1073/pnas.1707929115 schema:sameAs https://app.dimensions.ai/details/publication/pub.1101340662
    273 rdf:type schema:CreativeWork
    274 https://doi.org/10.1073/pnas.89.5.1875 schema:sameAs https://app.dimensions.ai/details/publication/pub.1008212871
    275 rdf:type schema:CreativeWork
    276 https://doi.org/10.1074/jbc.m113.477950 schema:sameAs https://app.dimensions.ai/details/publication/pub.1024286425
    277 rdf:type schema:CreativeWork
    278 https://doi.org/10.1074/jbc.m207573200 schema:sameAs https://app.dimensions.ai/details/publication/pub.1031827374
    279 rdf:type schema:CreativeWork
    280 https://doi.org/10.1074/jbc.m410994200 schema:sameAs https://app.dimensions.ai/details/publication/pub.1034431301
    281 rdf:type schema:CreativeWork
    282 https://doi.org/10.1093/carcin/bgn164 schema:sameAs https://app.dimensions.ai/details/publication/pub.1042640094
    283 rdf:type schema:CreativeWork
    284 https://doi.org/10.1093/embo-reports/kve177 schema:sameAs https://app.dimensions.ai/details/publication/pub.1019651123
    285 rdf:type schema:CreativeWork
    286 https://doi.org/10.1111/brv.12293 schema:sameAs https://app.dimensions.ai/details/publication/pub.1025990254
    287 rdf:type schema:CreativeWork
    288 https://doi.org/10.1126/science.274.5288.787 schema:sameAs https://app.dimensions.ai/details/publication/pub.1062554673
    289 rdf:type schema:CreativeWork
    290 https://doi.org/10.1126/scisignal.aaa3206 schema:sameAs https://app.dimensions.ai/details/publication/pub.1062685422
    291 rdf:type schema:CreativeWork
    292 https://doi.org/10.1128/mcb.25.1.336-345.2005 schema:sameAs https://app.dimensions.ai/details/publication/pub.1039090002
    293 rdf:type schema:CreativeWork
    294 https://doi.org/10.1158/0008-5472.can-06-3126 schema:sameAs https://app.dimensions.ai/details/publication/pub.1010617336
    295 rdf:type schema:CreativeWork
    296 https://doi.org/10.1158/0008-5472.can-08-4418 schema:sameAs https://app.dimensions.ai/details/publication/pub.1051237515
    297 rdf:type schema:CreativeWork
    298 https://doi.org/10.1158/0008-5472.can-10-0732 schema:sameAs https://app.dimensions.ai/details/publication/pub.1012806954
    299 rdf:type schema:CreativeWork
    300 https://doi.org/10.1158/0008-5472.can-11-0221 schema:sameAs https://app.dimensions.ai/details/publication/pub.1040716811
    301 rdf:type schema:CreativeWork
    302 https://doi.org/10.1158/0008-5472.can-14-0013 schema:sameAs https://app.dimensions.ai/details/publication/pub.1041620473
    303 rdf:type schema:CreativeWork
    304 https://doi.org/10.1158/0008-5472.can-14-2430 schema:sameAs https://app.dimensions.ai/details/publication/pub.1063215741
    305 rdf:type schema:CreativeWork
    306 https://doi.org/10.1158/1078-0432.ccr-10-2743 schema:sameAs https://app.dimensions.ai/details/publication/pub.1053110288
    307 rdf:type schema:CreativeWork
    308 https://doi.org/10.1158/1541-7786.mcr-14-0604 schema:sameAs https://app.dimensions.ai/details/publication/pub.1039577003
    309 rdf:type schema:CreativeWork
    310 https://doi.org/10.1159/000085964 schema:sameAs https://app.dimensions.ai/details/publication/pub.1006357405
    311 rdf:type schema:CreativeWork
    312 https://doi.org/10.1182/blood-2009-04-217042 schema:sameAs https://app.dimensions.ai/details/publication/pub.1010448675
    313 rdf:type schema:CreativeWork
    314 https://doi.org/10.1371/journal.pone.0002428 schema:sameAs https://app.dimensions.ai/details/publication/pub.1010141743
    315 rdf:type schema:CreativeWork
    316 https://doi.org/10.1371/journal.pone.0061948 schema:sameAs https://app.dimensions.ai/details/publication/pub.1038032957
    317 rdf:type schema:CreativeWork
    318 https://doi.org/10.1523/jneurosci.3324-13.2014 schema:sameAs https://app.dimensions.ai/details/publication/pub.1032920419
    319 rdf:type schema:CreativeWork
    320 https://doi.org/10.1523/jneurosci.3745-14.2015 schema:sameAs https://app.dimensions.ai/details/publication/pub.1032506018
    321 rdf:type schema:CreativeWork
    322 https://doi.org/10.18632/oncotarget.23305 schema:sameAs https://app.dimensions.ai/details/publication/pub.1099685649
    323 rdf:type schema:CreativeWork
    324 https://doi.org/10.18632/oncotarget.5337 schema:sameAs https://app.dimensions.ai/details/publication/pub.1020530123
    325 rdf:type schema:CreativeWork
    326 https://doi.org/10.18632/oncotarget.9107 schema:sameAs https://app.dimensions.ai/details/publication/pub.1046445029
    327 rdf:type schema:CreativeWork
    328 https://doi.org/10.3389/fonc.2018.00166 schema:sameAs https://app.dimensions.ai/details/publication/pub.1104037395
    329 rdf:type schema:CreativeWork
    330 https://doi.org/10.3390/ijms140510143 schema:sameAs https://app.dimensions.ai/details/publication/pub.1051934526
    331 rdf:type schema:CreativeWork
    332 https://doi.org/10.3892/ol.2016.4937 schema:sameAs https://app.dimensions.ai/details/publication/pub.1071527696
    333 rdf:type schema:CreativeWork
    334 https://www.grid.ac/institutes/grid.9983.b schema:alternateName University of Lisbon
    335 schema:name Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Lisbon, Portugal
    336 rdf:type schema:Organization
     




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


    ...