Lysosomal trapping of palbociclib and its functional implications View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2019-01-28

AUTHORS

Susana Llanos, Diego Megias, Carmen Blanco-Aparicio, Elena Hernández-Encinas, Miguel Rovira, Federico Pietrocola, Manuel Serrano

ABSTRACT

Palbociclib is a selective inhibitor of cyclin-dependent kinases 4 and 6 (CDK4/6) approved for the treatment of some cancers. The main mechanism of action of palbociclib is to induce cell cycle arrest and senescence on responsive cells. Here, we report that palbociclib concentrates in intracellular acidic vesicles, where it can be readily observed due to its intrinsic fluorescence, and it is released from these vesicles upon dilution or washing out of the extracellular medium. This reversible storage of drugs into acidic vesicles is generally known as lysosomal trapping and, based on this, we uncover novel properties of palbociclib. In particular, a short exposure of cells to palbociclib is sufficient to produce a stable cell-cycle arrest and long-term senescence. Moreover, after washing out the drug, palbociclib-treated cells release the drug to the medium and this conditioned medium is active on susceptible cells. Interestingly, cancer cells resistant to palbociclib also accumulate and release the drug producing paracrine senescence on susceptible cells. Finally, other lysosomotropic drugs, such as chloroquine, interfere with the accumulation of palbociclib into lysosomes, thereby reducing the minimal dose of palbociclib required for cell-cycle arrest and senescence. In summary, lysosomal trapping explains the prolonged temporal activity of palbociclib, the paracrine activity of exposed cells, and the cooperation with lysosomotropic drugs. These are important features that may help to improve the therapeutic dosing and efficacy of palbociclib. Finally, two other clinically approved CDK4/6 inhibitors, ribociclib and abemaciclib, present a similar behavior as palbociclib, suggesting that lysosomal trapping is a property common to all three clinically-approved CDK4/6 inhibitors. More... »

PAGES

1-17

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s41388-019-0695-8

DOI

http://dx.doi.org/10.1038/s41388-019-0695-8

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1111670119

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/30692638


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

JSON-LD is the canonical representation for SciGraph data.

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

[
  {
    "@context": "https://springernature.github.io/scigraph/jsonld/sgcontext.json", 
    "about": [
      {
        "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/0601", 
        "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
        "name": "Biochemistry and Cell Biology", 
        "type": "DefinedTerm"
      }, 
      {
        "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/06", 
        "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
        "name": "Biological Sciences", 
        "type": "DefinedTerm"
      }
    ], 
    "author": [
      {
        "affiliation": {
          "alternateName": "Spanish National Cancer Research Centre", 
          "id": "https://www.grid.ac/institutes/grid.7719.8", 
          "name": [
            "Spanish National Cancer Research Center (CNIO), Madrid, Spain"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Llanos", 
        "givenName": "Susana", 
        "id": "sg:person.01001613076.11", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01001613076.11"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Spanish National Cancer Research Centre", 
          "id": "https://www.grid.ac/institutes/grid.7719.8", 
          "name": [
            "Spanish National Cancer Research Center (CNIO), Madrid, Spain"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Megias", 
        "givenName": "Diego", 
        "id": "sg:person.0612602655.65", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0612602655.65"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Spanish National Cancer Research Centre", 
          "id": "https://www.grid.ac/institutes/grid.7719.8", 
          "name": [
            "Spanish National Cancer Research Center (CNIO), Madrid, Spain"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Blanco-Aparicio", 
        "givenName": "Carmen", 
        "id": "sg:person.01300502421.68", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01300502421.68"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Spanish National Cancer Research Centre", 
          "id": "https://www.grid.ac/institutes/grid.7719.8", 
          "name": [
            "Spanish National Cancer Research Center (CNIO), Madrid, Spain"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Hern\u00e1ndez-Encinas", 
        "givenName": "Elena", 
        "id": "sg:person.0654606734.15", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0654606734.15"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Institute for Research in Biomedicine", 
          "id": "https://www.grid.ac/institutes/grid.7722.0", 
          "name": [
            "Institute for Research in Biomedicine (IRB Barcelona), Barcelona Institute of Science and Technology (BIST), Barcelona, Spain"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Rovira", 
        "givenName": "Miguel", 
        "id": "sg:person.014667544571.55", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.014667544571.55"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Institute for Research in Biomedicine", 
          "id": "https://www.grid.ac/institutes/grid.7722.0", 
          "name": [
            "Institute for Research in Biomedicine (IRB Barcelona), Barcelona Institute of Science and Technology (BIST), Barcelona, Spain"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Pietrocola", 
        "givenName": "Federico", 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Instituci\u00f3 Catalana de Recerca i Estudis Avan\u00e7ats", 
          "id": "https://www.grid.ac/institutes/grid.425902.8", 
          "name": [
            "Spanish National Cancer Research Center (CNIO), Madrid, Spain", 
            "Institute for Research in Biomedicine (IRB Barcelona), Barcelona Institute of Science and Technology (BIST), Barcelona, Spain", 
            "Catalan Institution for Research and Advanced Studies (ICREA), Barcelona, Spain"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Serrano", 
        "givenName": "Manuel", 
        "id": "sg:person.013110175140.37", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.013110175140.37"
        ], 
        "type": "Person"
      }
    ], 
    "citation": [
      {
        "id": "https://doi.org/10.1124/jpet.109.160226", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1000505577"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1002/cyto.a.22495", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1002871105"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1124/dmd.109.027888", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1002992055"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/s0278-5846(02)00317-2", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1004012002"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/s0278-5846(02)00317-2", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1004012002"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/s0924-977x(99)00034-6", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1004599303"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1002/1097-0142(19910601)67:11<2741::aid-cncr2820671105>3.0.co;2-s", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1006554732"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1093/jnci/djq364", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1009713990"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/s0076-6879(08)03612-4", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1010287224"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1046/j.1365-2184.1996.01009.x", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1014405256"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1111/j.1600-0773.1997.tb00285.x", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1015574966"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1111/j.1600-0773.1997.tb00285.x", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1015574966"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/s0092-8674(03)00401-x", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1018706213"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1371/journal.pone.0078641", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1019516413"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1073/pnas.92.20.9363", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1021293422"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1517/17425255.2012.691165", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1021481894"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.18632/oncotarget.4836", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1021871447"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.tcb.2011.11.006", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1022147352"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1007/bf01218360", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1026107781", 
          "https://doi.org/10.1007/bf01218360"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1007/bf01218360", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1026107781", 
          "https://doi.org/10.1007/bf01218360"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1073/pnas.92.22.10436", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1026715271"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.drup.2015.11.004", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1027719327"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1124/dmd.112.050054", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1028359825"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/ncb3225", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1028769870", 
          "https://doi.org/10.1038/ncb3225"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1128/mcb.22.10.3497-3508.2002", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1030694627"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.4155/bio.09.128", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1032861671"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.molmed.2010.03.003", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1033625660"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1080/1744666x.2016.1212659", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1034870568"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/onc.2011.277", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1036087824", 
          "https://doi.org/10.1038/onc.2011.277"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.ejpb.2006.06.005", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1039265908"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1126/science.1218351", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1041565158"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1158/1078-0432.ccr-14-0816", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1043466683"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/ncb3195", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1047010141", 
          "https://doi.org/10.1038/ncb3195"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1002/jps.20530", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1048205547"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1001/archotol.1994.01880310054010", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1048495771"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1002/bod.2510090602", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1049940157"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1186/bcr2419", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1050281960", 
          "https://doi.org/10.1186/bcr2419"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.ccr.2011.10.001", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1052152545"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nrm3823", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1053250436", 
          "https://doi.org/10.1038/nrm3823"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1158/1078-0432.ccr-15-1185", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1063224989"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.2174/1871520615666151019092919", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1069219224"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.4161/cc.26130", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1072297354"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.5603/fhc.2012.0031", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1073038008"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://app.dimensions.ai/details/publication/pub.1074708302", 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.phrs.2017.02.013", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1083830231"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1111/bph.13836", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1085201187"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1111/bph.13836", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1085201187"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nature22797", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1085870242", 
          "https://doi.org/10.1038/nature22797"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nature22797", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1085870242", 
          "https://doi.org/10.1038/nature22797"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/ncomms15916", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1086283445", 
          "https://doi.org/10.1038/ncomms15916"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nature23465", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1091217490", 
          "https://doi.org/10.1038/nature23465"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nature23465", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1091217490", 
          "https://doi.org/10.1038/nature23465"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.yexcr.2017.09.031", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1091904426"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.tcb.2018.02.001", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1101148560"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.15252/embj.201798359", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1103449115"
        ], 
        "type": "CreativeWork"
      }
    ], 
    "datePublished": "2019-01-28", 
    "datePublishedReg": "2019-01-28", 
    "description": "Palbociclib is a selective inhibitor of cyclin-dependent kinases 4 and 6 (CDK4/6) approved for the treatment of some cancers. The main mechanism of action of palbociclib is to induce cell cycle arrest and senescence on responsive cells. Here, we report that palbociclib concentrates in intracellular acidic vesicles, where it can be readily observed due to its intrinsic fluorescence, and it is released from these vesicles upon dilution or washing out of the extracellular medium. This reversible storage of drugs into acidic vesicles is generally known as lysosomal trapping and, based on this, we uncover novel properties of palbociclib. In particular, a short exposure of cells to palbociclib is sufficient to produce a stable cell-cycle arrest and long-term senescence. Moreover, after washing out the drug, palbociclib-treated cells release the drug to the medium and this conditioned medium is active on susceptible cells. Interestingly, cancer cells resistant to palbociclib also accumulate and release the drug producing paracrine senescence on susceptible cells. Finally, other lysosomotropic drugs, such as chloroquine, interfere with the accumulation of palbociclib into lysosomes, thereby reducing the minimal dose of palbociclib required for cell-cycle arrest and senescence. In summary, lysosomal trapping explains the prolonged temporal activity of palbociclib, the paracrine activity of exposed cells, and the cooperation with lysosomotropic drugs. These are important features that may help to improve the therapeutic dosing and efficacy of palbociclib. Finally, two other clinically approved CDK4/6 inhibitors, ribociclib and abemaciclib, present a similar behavior as palbociclib, suggesting that lysosomal trapping is a property common to all three clinically-approved CDK4/6 inhibitors.", 
    "genre": "research_article", 
    "id": "sg:pub.10.1038/s41388-019-0695-8", 
    "inLanguage": [
      "en"
    ], 
    "isAccessibleForFree": false, 
    "isPartOf": [
      {
        "id": "sg:journal.1097543", 
        "issn": [
          "0950-9232", 
          "1476-5594"
        ], 
        "name": "Oncogene", 
        "type": "Periodical"
      }
    ], 
    "name": "Lysosomal trapping of palbociclib and its functional implications", 
    "pagination": "1-17", 
    "productId": [
      {
        "name": "readcube_id", 
        "type": "PropertyValue", 
        "value": [
          "1e76fc972cf1929a93b47cd68e47fa92754f58bfea7b59f32a6be35c017624df"
        ]
      }, 
      {
        "name": "pubmed_id", 
        "type": "PropertyValue", 
        "value": [
          "30692638"
        ]
      }, 
      {
        "name": "nlm_unique_id", 
        "type": "PropertyValue", 
        "value": [
          "8711562"
        ]
      }, 
      {
        "name": "doi", 
        "type": "PropertyValue", 
        "value": [
          "10.1038/s41388-019-0695-8"
        ]
      }, 
      {
        "name": "dimensions_id", 
        "type": "PropertyValue", 
        "value": [
          "pub.1111670119"
        ]
      }
    ], 
    "sameAs": [
      "https://doi.org/10.1038/s41388-019-0695-8", 
      "https://app.dimensions.ai/details/publication/pub.1111670119"
    ], 
    "sdDataset": "articles", 
    "sdDatePublished": "2019-04-11T09:57", 
    "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/v90/0000000347_0000000347/records_89807_00000004.jsonl", 
    "type": "ScholarlyArticle", 
    "url": "https://www.nature.com/articles/s41388-019-0695-8"
  }
]
 

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/s41388-019-0695-8'

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/s41388-019-0695-8'

Turtle is a human-readable linked data format.

curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1038/s41388-019-0695-8'

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

curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1038/s41388-019-0695-8'


 

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

267 TRIPLES      21 PREDICATES      75 URIs      18 LITERALS      7 BLANK NODES

Subject Predicate Object
1 sg:pub.10.1038/s41388-019-0695-8 schema:about anzsrc-for:06
2 anzsrc-for:0601
3 schema:author N1ff688b12a194b9c8dbbd7e9b78e0a3d
4 schema:citation sg:pub.10.1007/bf01218360
5 sg:pub.10.1038/nature22797
6 sg:pub.10.1038/nature23465
7 sg:pub.10.1038/ncb3195
8 sg:pub.10.1038/ncb3225
9 sg:pub.10.1038/ncomms15916
10 sg:pub.10.1038/nrm3823
11 sg:pub.10.1038/onc.2011.277
12 sg:pub.10.1186/bcr2419
13 https://app.dimensions.ai/details/publication/pub.1074708302
14 https://doi.org/10.1001/archotol.1994.01880310054010
15 https://doi.org/10.1002/1097-0142(19910601)67:11<2741::aid-cncr2820671105>3.0.co;2-s
16 https://doi.org/10.1002/bod.2510090602
17 https://doi.org/10.1002/cyto.a.22495
18 https://doi.org/10.1002/jps.20530
19 https://doi.org/10.1016/j.ccr.2011.10.001
20 https://doi.org/10.1016/j.drup.2015.11.004
21 https://doi.org/10.1016/j.ejpb.2006.06.005
22 https://doi.org/10.1016/j.molmed.2010.03.003
23 https://doi.org/10.1016/j.phrs.2017.02.013
24 https://doi.org/10.1016/j.tcb.2011.11.006
25 https://doi.org/10.1016/j.tcb.2018.02.001
26 https://doi.org/10.1016/j.yexcr.2017.09.031
27 https://doi.org/10.1016/s0076-6879(08)03612-4
28 https://doi.org/10.1016/s0092-8674(03)00401-x
29 https://doi.org/10.1016/s0278-5846(02)00317-2
30 https://doi.org/10.1016/s0924-977x(99)00034-6
31 https://doi.org/10.1046/j.1365-2184.1996.01009.x
32 https://doi.org/10.1073/pnas.92.20.9363
33 https://doi.org/10.1073/pnas.92.22.10436
34 https://doi.org/10.1080/1744666x.2016.1212659
35 https://doi.org/10.1093/jnci/djq364
36 https://doi.org/10.1111/bph.13836
37 https://doi.org/10.1111/j.1600-0773.1997.tb00285.x
38 https://doi.org/10.1124/dmd.109.027888
39 https://doi.org/10.1124/dmd.112.050054
40 https://doi.org/10.1124/jpet.109.160226
41 https://doi.org/10.1126/science.1218351
42 https://doi.org/10.1128/mcb.22.10.3497-3508.2002
43 https://doi.org/10.1158/1078-0432.ccr-14-0816
44 https://doi.org/10.1158/1078-0432.ccr-15-1185
45 https://doi.org/10.1371/journal.pone.0078641
46 https://doi.org/10.1517/17425255.2012.691165
47 https://doi.org/10.15252/embj.201798359
48 https://doi.org/10.18632/oncotarget.4836
49 https://doi.org/10.2174/1871520615666151019092919
50 https://doi.org/10.4155/bio.09.128
51 https://doi.org/10.4161/cc.26130
52 https://doi.org/10.5603/fhc.2012.0031
53 schema:datePublished 2019-01-28
54 schema:datePublishedReg 2019-01-28
55 schema:description Palbociclib is a selective inhibitor of cyclin-dependent kinases 4 and 6 (CDK4/6) approved for the treatment of some cancers. The main mechanism of action of palbociclib is to induce cell cycle arrest and senescence on responsive cells. Here, we report that palbociclib concentrates in intracellular acidic vesicles, where it can be readily observed due to its intrinsic fluorescence, and it is released from these vesicles upon dilution or washing out of the extracellular medium. This reversible storage of drugs into acidic vesicles is generally known as lysosomal trapping and, based on this, we uncover novel properties of palbociclib. In particular, a short exposure of cells to palbociclib is sufficient to produce a stable cell-cycle arrest and long-term senescence. Moreover, after washing out the drug, palbociclib-treated cells release the drug to the medium and this conditioned medium is active on susceptible cells. Interestingly, cancer cells resistant to palbociclib also accumulate and release the drug producing paracrine senescence on susceptible cells. Finally, other lysosomotropic drugs, such as chloroquine, interfere with the accumulation of palbociclib into lysosomes, thereby reducing the minimal dose of palbociclib required for cell-cycle arrest and senescence. In summary, lysosomal trapping explains the prolonged temporal activity of palbociclib, the paracrine activity of exposed cells, and the cooperation with lysosomotropic drugs. These are important features that may help to improve the therapeutic dosing and efficacy of palbociclib. Finally, two other clinically approved CDK4/6 inhibitors, ribociclib and abemaciclib, present a similar behavior as palbociclib, suggesting that lysosomal trapping is a property common to all three clinically-approved CDK4/6 inhibitors.
56 schema:genre research_article
57 schema:inLanguage en
58 schema:isAccessibleForFree false
59 schema:isPartOf sg:journal.1097543
60 schema:name Lysosomal trapping of palbociclib and its functional implications
61 schema:pagination 1-17
62 schema:productId N4dceb8208a9042c3b8e53fd98e28459c
63 N5a039280f3dd4a40b93fa04f349c835f
64 N7f987396c8b04a9c9667f60de89097b9
65 N8858966971c84d4195611e66fc1ab052
66 Nb3227f3ee53548bc8adf768c571dc327
67 schema:sameAs https://app.dimensions.ai/details/publication/pub.1111670119
68 https://doi.org/10.1038/s41388-019-0695-8
69 schema:sdDatePublished 2019-04-11T09:57
70 schema:sdLicense https://scigraph.springernature.com/explorer/license/
71 schema:sdPublisher N56e18b9f130144919afe4672de55a54e
72 schema:url https://www.nature.com/articles/s41388-019-0695-8
73 sgo:license sg:explorer/license/
74 sgo:sdDataset articles
75 rdf:type schema:ScholarlyArticle
76 N083aca5436f441a580c1d26992b63b80 schema:affiliation https://www.grid.ac/institutes/grid.7722.0
77 schema:familyName Pietrocola
78 schema:givenName Federico
79 rdf:type schema:Person
80 N1ff688b12a194b9c8dbbd7e9b78e0a3d rdf:first sg:person.01001613076.11
81 rdf:rest Ne56c6e48d54c46ee88eb6c784dfe61ea
82 N2277b54a8967405486c84f2d12fddb5a rdf:first sg:person.013110175140.37
83 rdf:rest rdf:nil
84 N22eb470e12a34be08803679d26a85271 rdf:first sg:person.014667544571.55
85 rdf:rest Nf8e24ca59248435486847452d21b3704
86 N4105599233044c678d85c9042c59afd5 rdf:first sg:person.01300502421.68
87 rdf:rest N5b2f88ac247e49b495caa459e6dea85a
88 N4dceb8208a9042c3b8e53fd98e28459c schema:name nlm_unique_id
89 schema:value 8711562
90 rdf:type schema:PropertyValue
91 N56e18b9f130144919afe4672de55a54e schema:name Springer Nature - SN SciGraph project
92 rdf:type schema:Organization
93 N5a039280f3dd4a40b93fa04f349c835f schema:name pubmed_id
94 schema:value 30692638
95 rdf:type schema:PropertyValue
96 N5b2f88ac247e49b495caa459e6dea85a rdf:first sg:person.0654606734.15
97 rdf:rest N22eb470e12a34be08803679d26a85271
98 N7f987396c8b04a9c9667f60de89097b9 schema:name dimensions_id
99 schema:value pub.1111670119
100 rdf:type schema:PropertyValue
101 N8858966971c84d4195611e66fc1ab052 schema:name doi
102 schema:value 10.1038/s41388-019-0695-8
103 rdf:type schema:PropertyValue
104 Nb3227f3ee53548bc8adf768c571dc327 schema:name readcube_id
105 schema:value 1e76fc972cf1929a93b47cd68e47fa92754f58bfea7b59f32a6be35c017624df
106 rdf:type schema:PropertyValue
107 Ne56c6e48d54c46ee88eb6c784dfe61ea rdf:first sg:person.0612602655.65
108 rdf:rest N4105599233044c678d85c9042c59afd5
109 Nf8e24ca59248435486847452d21b3704 rdf:first N083aca5436f441a580c1d26992b63b80
110 rdf:rest N2277b54a8967405486c84f2d12fddb5a
111 anzsrc-for:06 schema:inDefinedTermSet anzsrc-for:
112 schema:name Biological Sciences
113 rdf:type schema:DefinedTerm
114 anzsrc-for:0601 schema:inDefinedTermSet anzsrc-for:
115 schema:name Biochemistry and Cell Biology
116 rdf:type schema:DefinedTerm
117 sg:journal.1097543 schema:issn 0950-9232
118 1476-5594
119 schema:name Oncogene
120 rdf:type schema:Periodical
121 sg:person.01001613076.11 schema:affiliation https://www.grid.ac/institutes/grid.7719.8
122 schema:familyName Llanos
123 schema:givenName Susana
124 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01001613076.11
125 rdf:type schema:Person
126 sg:person.01300502421.68 schema:affiliation https://www.grid.ac/institutes/grid.7719.8
127 schema:familyName Blanco-Aparicio
128 schema:givenName Carmen
129 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01300502421.68
130 rdf:type schema:Person
131 sg:person.013110175140.37 schema:affiliation https://www.grid.ac/institutes/grid.425902.8
132 schema:familyName Serrano
133 schema:givenName Manuel
134 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.013110175140.37
135 rdf:type schema:Person
136 sg:person.014667544571.55 schema:affiliation https://www.grid.ac/institutes/grid.7722.0
137 schema:familyName Rovira
138 schema:givenName Miguel
139 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.014667544571.55
140 rdf:type schema:Person
141 sg:person.0612602655.65 schema:affiliation https://www.grid.ac/institutes/grid.7719.8
142 schema:familyName Megias
143 schema:givenName Diego
144 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0612602655.65
145 rdf:type schema:Person
146 sg:person.0654606734.15 schema:affiliation https://www.grid.ac/institutes/grid.7719.8
147 schema:familyName Hernández-Encinas
148 schema:givenName Elena
149 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0654606734.15
150 rdf:type schema:Person
151 sg:pub.10.1007/bf01218360 schema:sameAs https://app.dimensions.ai/details/publication/pub.1026107781
152 https://doi.org/10.1007/bf01218360
153 rdf:type schema:CreativeWork
154 sg:pub.10.1038/nature22797 schema:sameAs https://app.dimensions.ai/details/publication/pub.1085870242
155 https://doi.org/10.1038/nature22797
156 rdf:type schema:CreativeWork
157 sg:pub.10.1038/nature23465 schema:sameAs https://app.dimensions.ai/details/publication/pub.1091217490
158 https://doi.org/10.1038/nature23465
159 rdf:type schema:CreativeWork
160 sg:pub.10.1038/ncb3195 schema:sameAs https://app.dimensions.ai/details/publication/pub.1047010141
161 https://doi.org/10.1038/ncb3195
162 rdf:type schema:CreativeWork
163 sg:pub.10.1038/ncb3225 schema:sameAs https://app.dimensions.ai/details/publication/pub.1028769870
164 https://doi.org/10.1038/ncb3225
165 rdf:type schema:CreativeWork
166 sg:pub.10.1038/ncomms15916 schema:sameAs https://app.dimensions.ai/details/publication/pub.1086283445
167 https://doi.org/10.1038/ncomms15916
168 rdf:type schema:CreativeWork
169 sg:pub.10.1038/nrm3823 schema:sameAs https://app.dimensions.ai/details/publication/pub.1053250436
170 https://doi.org/10.1038/nrm3823
171 rdf:type schema:CreativeWork
172 sg:pub.10.1038/onc.2011.277 schema:sameAs https://app.dimensions.ai/details/publication/pub.1036087824
173 https://doi.org/10.1038/onc.2011.277
174 rdf:type schema:CreativeWork
175 sg:pub.10.1186/bcr2419 schema:sameAs https://app.dimensions.ai/details/publication/pub.1050281960
176 https://doi.org/10.1186/bcr2419
177 rdf:type schema:CreativeWork
178 https://app.dimensions.ai/details/publication/pub.1074708302 schema:CreativeWork
179 https://doi.org/10.1001/archotol.1994.01880310054010 schema:sameAs https://app.dimensions.ai/details/publication/pub.1048495771
180 rdf:type schema:CreativeWork
181 https://doi.org/10.1002/1097-0142(19910601)67:11<2741::aid-cncr2820671105>3.0.co;2-s schema:sameAs https://app.dimensions.ai/details/publication/pub.1006554732
182 rdf:type schema:CreativeWork
183 https://doi.org/10.1002/bod.2510090602 schema:sameAs https://app.dimensions.ai/details/publication/pub.1049940157
184 rdf:type schema:CreativeWork
185 https://doi.org/10.1002/cyto.a.22495 schema:sameAs https://app.dimensions.ai/details/publication/pub.1002871105
186 rdf:type schema:CreativeWork
187 https://doi.org/10.1002/jps.20530 schema:sameAs https://app.dimensions.ai/details/publication/pub.1048205547
188 rdf:type schema:CreativeWork
189 https://doi.org/10.1016/j.ccr.2011.10.001 schema:sameAs https://app.dimensions.ai/details/publication/pub.1052152545
190 rdf:type schema:CreativeWork
191 https://doi.org/10.1016/j.drup.2015.11.004 schema:sameAs https://app.dimensions.ai/details/publication/pub.1027719327
192 rdf:type schema:CreativeWork
193 https://doi.org/10.1016/j.ejpb.2006.06.005 schema:sameAs https://app.dimensions.ai/details/publication/pub.1039265908
194 rdf:type schema:CreativeWork
195 https://doi.org/10.1016/j.molmed.2010.03.003 schema:sameAs https://app.dimensions.ai/details/publication/pub.1033625660
196 rdf:type schema:CreativeWork
197 https://doi.org/10.1016/j.phrs.2017.02.013 schema:sameAs https://app.dimensions.ai/details/publication/pub.1083830231
198 rdf:type schema:CreativeWork
199 https://doi.org/10.1016/j.tcb.2011.11.006 schema:sameAs https://app.dimensions.ai/details/publication/pub.1022147352
200 rdf:type schema:CreativeWork
201 https://doi.org/10.1016/j.tcb.2018.02.001 schema:sameAs https://app.dimensions.ai/details/publication/pub.1101148560
202 rdf:type schema:CreativeWork
203 https://doi.org/10.1016/j.yexcr.2017.09.031 schema:sameAs https://app.dimensions.ai/details/publication/pub.1091904426
204 rdf:type schema:CreativeWork
205 https://doi.org/10.1016/s0076-6879(08)03612-4 schema:sameAs https://app.dimensions.ai/details/publication/pub.1010287224
206 rdf:type schema:CreativeWork
207 https://doi.org/10.1016/s0092-8674(03)00401-x schema:sameAs https://app.dimensions.ai/details/publication/pub.1018706213
208 rdf:type schema:CreativeWork
209 https://doi.org/10.1016/s0278-5846(02)00317-2 schema:sameAs https://app.dimensions.ai/details/publication/pub.1004012002
210 rdf:type schema:CreativeWork
211 https://doi.org/10.1016/s0924-977x(99)00034-6 schema:sameAs https://app.dimensions.ai/details/publication/pub.1004599303
212 rdf:type schema:CreativeWork
213 https://doi.org/10.1046/j.1365-2184.1996.01009.x schema:sameAs https://app.dimensions.ai/details/publication/pub.1014405256
214 rdf:type schema:CreativeWork
215 https://doi.org/10.1073/pnas.92.20.9363 schema:sameAs https://app.dimensions.ai/details/publication/pub.1021293422
216 rdf:type schema:CreativeWork
217 https://doi.org/10.1073/pnas.92.22.10436 schema:sameAs https://app.dimensions.ai/details/publication/pub.1026715271
218 rdf:type schema:CreativeWork
219 https://doi.org/10.1080/1744666x.2016.1212659 schema:sameAs https://app.dimensions.ai/details/publication/pub.1034870568
220 rdf:type schema:CreativeWork
221 https://doi.org/10.1093/jnci/djq364 schema:sameAs https://app.dimensions.ai/details/publication/pub.1009713990
222 rdf:type schema:CreativeWork
223 https://doi.org/10.1111/bph.13836 schema:sameAs https://app.dimensions.ai/details/publication/pub.1085201187
224 rdf:type schema:CreativeWork
225 https://doi.org/10.1111/j.1600-0773.1997.tb00285.x schema:sameAs https://app.dimensions.ai/details/publication/pub.1015574966
226 rdf:type schema:CreativeWork
227 https://doi.org/10.1124/dmd.109.027888 schema:sameAs https://app.dimensions.ai/details/publication/pub.1002992055
228 rdf:type schema:CreativeWork
229 https://doi.org/10.1124/dmd.112.050054 schema:sameAs https://app.dimensions.ai/details/publication/pub.1028359825
230 rdf:type schema:CreativeWork
231 https://doi.org/10.1124/jpet.109.160226 schema:sameAs https://app.dimensions.ai/details/publication/pub.1000505577
232 rdf:type schema:CreativeWork
233 https://doi.org/10.1126/science.1218351 schema:sameAs https://app.dimensions.ai/details/publication/pub.1041565158
234 rdf:type schema:CreativeWork
235 https://doi.org/10.1128/mcb.22.10.3497-3508.2002 schema:sameAs https://app.dimensions.ai/details/publication/pub.1030694627
236 rdf:type schema:CreativeWork
237 https://doi.org/10.1158/1078-0432.ccr-14-0816 schema:sameAs https://app.dimensions.ai/details/publication/pub.1043466683
238 rdf:type schema:CreativeWork
239 https://doi.org/10.1158/1078-0432.ccr-15-1185 schema:sameAs https://app.dimensions.ai/details/publication/pub.1063224989
240 rdf:type schema:CreativeWork
241 https://doi.org/10.1371/journal.pone.0078641 schema:sameAs https://app.dimensions.ai/details/publication/pub.1019516413
242 rdf:type schema:CreativeWork
243 https://doi.org/10.1517/17425255.2012.691165 schema:sameAs https://app.dimensions.ai/details/publication/pub.1021481894
244 rdf:type schema:CreativeWork
245 https://doi.org/10.15252/embj.201798359 schema:sameAs https://app.dimensions.ai/details/publication/pub.1103449115
246 rdf:type schema:CreativeWork
247 https://doi.org/10.18632/oncotarget.4836 schema:sameAs https://app.dimensions.ai/details/publication/pub.1021871447
248 rdf:type schema:CreativeWork
249 https://doi.org/10.2174/1871520615666151019092919 schema:sameAs https://app.dimensions.ai/details/publication/pub.1069219224
250 rdf:type schema:CreativeWork
251 https://doi.org/10.4155/bio.09.128 schema:sameAs https://app.dimensions.ai/details/publication/pub.1032861671
252 rdf:type schema:CreativeWork
253 https://doi.org/10.4161/cc.26130 schema:sameAs https://app.dimensions.ai/details/publication/pub.1072297354
254 rdf:type schema:CreativeWork
255 https://doi.org/10.5603/fhc.2012.0031 schema:sameAs https://app.dimensions.ai/details/publication/pub.1073038008
256 rdf:type schema:CreativeWork
257 https://www.grid.ac/institutes/grid.425902.8 schema:alternateName Institució Catalana de Recerca i Estudis Avançats
258 schema:name Catalan Institution for Research and Advanced Studies (ICREA), Barcelona, Spain
259 Institute for Research in Biomedicine (IRB Barcelona), Barcelona Institute of Science and Technology (BIST), Barcelona, Spain
260 Spanish National Cancer Research Center (CNIO), Madrid, Spain
261 rdf:type schema:Organization
262 https://www.grid.ac/institutes/grid.7719.8 schema:alternateName Spanish National Cancer Research Centre
263 schema:name Spanish National Cancer Research Center (CNIO), Madrid, Spain
264 rdf:type schema:Organization
265 https://www.grid.ac/institutes/grid.7722.0 schema:alternateName Institute for Research in Biomedicine
266 schema:name Institute for Research in Biomedicine (IRB Barcelona), Barcelona Institute of Science and Technology (BIST), Barcelona, Spain
267 rdf:type schema:Organization
 




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


...