Glutamine synthetase is necessary for sarcoma adaptation to glutamine deprivation and tumor growth View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2019-03

AUTHORS

Sameer H. Issaq, Arnulfo Mendoza, Stephen D. Fox, Lee J. Helman

ABSTRACT

Despite a growing body of knowledge about the genomic landscape and molecular pathogenesis of sarcomas, translation of basic discoveries into targeted therapies and significant clinical gains has remained elusive. Renewed interest in altered metabolic properties of cancer cells has led to an exploration of targeting metabolic dependencies as a novel therapeutic strategy. In this study, we have characterized the dependency of human pediatric sarcoma cells on key metabolic substrates and identified a mechanism of adaptation to metabolic stress by examining proliferation and bioenergetic properties of rhabdomyosarcoma and Ewing sarcoma cells under varying concentrations of glucose and glutamine. While all cell lines tested were completely growth-inhibited by lack of glucose, cells adapted to glutamine deprivation, and restored proliferation following an initial period of reduced growth. We show that expression of glutamine synthetase (GS), the enzyme responsible for de novo glutamine synthesis, increased during glutamine deprivation, and that pharmacological or shRNA-mediated GS inhibition abolished proliferation of glutamine-deprived cells, while having no effect on cells grown under normal culture conditions. Moreover, the GS substrates and glutamine precursors glutamate and ammonia restored proliferation of glutamine-deprived cells in a GS-dependent manner, further emphasizing the necessity of GS for adaptation to glutamine stress. Furthermore, pharmacological and shRNA-mediated GS inhibition significantly reduced orthotopic xenograft tumor growth. We also show that glutamine supports sarcoma nucleotide biosynthesis and optimal mitochondrial bioenergetics. Our findings demonstrate that GS mediates proliferation of glutamine-deprived pediatric sarcomas, and suggest that targeting metabolic dependencies of sarcomas should be further investigated as a potential therapeutic strategy. More... »

PAGES

20

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s41389-019-0129-z

DOI

http://dx.doi.org/10.1038/s41389-019-0129-z

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1112387989

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/30808861


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": "Center for Cancer Research", 
          "id": "https://www.grid.ac/institutes/grid.417768.b", 
          "name": [
            "Pediatric Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Issaq", 
        "givenName": "Sameer H.", 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Center for Cancer Research", 
          "id": "https://www.grid.ac/institutes/grid.417768.b", 
          "name": [
            "Pediatric Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Mendoza", 
        "givenName": "Arnulfo", 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Frederick National Laboratory for Cancer Research", 
          "id": "https://www.grid.ac/institutes/grid.418021.e", 
          "name": [
            "Protein Characterization Laboratory, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc., Frederick, MD, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Fox", 
        "givenName": "Stephen D.", 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Children's Hospital of Los Angeles", 
          "id": "https://www.grid.ac/institutes/grid.239546.f", 
          "name": [
            "Pediatric Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA", 
            "Departments of Pediatrics and Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA", 
            "Children\u2019s Center for Cancer and Blood Diseases, Children\u2019s Hospital Los Angeles, Los Angeles, CA, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Helman", 
        "givenName": "Lee J.", 
        "type": "Person"
      }
    ], 
    "citation": [
      {
        "id": "https://doi.org/10.3389/fonc.2015.00190", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1001649918"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.ijrobp.2014.08.005", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1003649526"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/bjc.2014.425", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1005692217", 
          "https://doi.org/10.1038/bjc.2014.425"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nrc1168", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1006265436", 
          "https://doi.org/10.1038/nrc1168"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nrc1168", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1006265436", 
          "https://doi.org/10.1038/nrc1168"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.cmet.2007.10.002", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1006428882"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.molcel.2016.02.032", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1006778665"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/ncomms11457", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1021043408", 
          "https://doi.org/10.1038/ncomms11457"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1186/2045-3329-2-14", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1021871767", 
          "https://doi.org/10.1186/2045-3329-2-14"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.cell.2011.02.013", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1023540354"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1097/rlu.0b013e318217ae2e", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1024829111"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1200/jco.2005.01.7079", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1026327123"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nrc3087", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1026938278", 
          "https://doi.org/10.1038/nrc3087"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.12688/f1000research.8631.1", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1027022849"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.12688/f1000research.8631.1", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1027022849"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nrd3504", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1028324544", 
          "https://doi.org/10.1038/nrd3504"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.4155/fmc.13.130", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1029120446"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.pharmthera.2012.10.004", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1029630083"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.cancergen.2016.03.004", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1031932079"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/ncb3272", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1032287924", 
          "https://doi.org/10.1038/ncb3272"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1126/science.1160809", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1033271739"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1126/science.1160809", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1033271739"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1101/cshperspect.a025650", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1033606975"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1172/jci69600", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1036293561"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1158/1078-0432.ccr-13-0633", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1037622162"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.cmet.2016.01.007", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1039310213"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/s0167-4838(99)00270-8", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1044614628"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nrc.2016.71", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1045229038", 
          "https://doi.org/10.1038/nrc.2016.71"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1053/j.semnuclmed.2016.12.004", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1045863211"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1007/s00259-002-0859-5", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1049393085", 
          "https://doi.org/10.1007/s00259-002-0859-5"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1155/2011/756982", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1052527823"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.cmet.2015.09.025", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1053690973"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.cmet.2015.09.025", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1053690973"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1615/critrevoncog.2015013553", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1068132376"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1615/critrevoncog.2015013800", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1068132382"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.2174/138955708785132800", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1069182928"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.4161/cc.28010", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1072297547"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.4161/cc.7.2.5229", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1072299672"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1080/14728222.2017.1303484", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1084165971"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.14694/edbk_175378", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1085765647"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.celrep.2017.07.054", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1091215778"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1158/1078-0432.ccr-17-1121", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1091621417"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.tcb.2017.11.006", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1099623945"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.tcb.2017.11.006", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1099623945"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.3390/genes9020108", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1101125257"
        ], 
        "type": "CreativeWork"
      }
    ], 
    "datePublished": "2019-03", 
    "datePublishedReg": "2019-03-01", 
    "description": "Despite a growing body of knowledge about the genomic landscape and molecular pathogenesis of sarcomas, translation of basic discoveries into targeted therapies and significant clinical gains has remained elusive. Renewed interest in altered metabolic properties of cancer cells has led to an exploration of targeting metabolic dependencies as a novel therapeutic strategy. In this study, we have characterized the dependency of human pediatric sarcoma cells on key metabolic substrates and identified a mechanism of adaptation to metabolic stress by examining proliferation and bioenergetic properties of rhabdomyosarcoma and Ewing sarcoma cells under varying concentrations of glucose and glutamine. While all cell lines tested were completely growth-inhibited by lack of glucose, cells adapted to glutamine deprivation, and restored proliferation following an initial period of reduced growth. We show that expression of glutamine synthetase (GS), the enzyme responsible for de novo glutamine synthesis, increased during glutamine deprivation, and that pharmacological or shRNA-mediated GS inhibition abolished proliferation of glutamine-deprived cells, while having no effect on cells grown under normal culture conditions. Moreover, the GS substrates and glutamine precursors glutamate and ammonia restored proliferation of glutamine-deprived cells in a GS-dependent manner, further emphasizing the necessity of GS for adaptation to glutamine stress. Furthermore, pharmacological and shRNA-mediated GS inhibition significantly reduced orthotopic xenograft tumor growth. We also show that glutamine supports sarcoma nucleotide biosynthesis and optimal mitochondrial bioenergetics. Our findings demonstrate that GS mediates proliferation of glutamine-deprived pediatric sarcomas, and suggest that targeting metabolic dependencies of sarcomas should be further investigated as a potential therapeutic strategy.", 
    "genre": "research_article", 
    "id": "sg:pub.10.1038/s41389-019-0129-z", 
    "inLanguage": [
      "en"
    ], 
    "isAccessibleForFree": false, 
    "isPartOf": [
      {
        "id": "sg:journal.1046557", 
        "issn": [
          "2157-9024"
        ], 
        "name": "Oncogenesis", 
        "type": "Periodical"
      }, 
      {
        "issueNumber": "3", 
        "type": "PublicationIssue"
      }, 
      {
        "type": "PublicationVolume", 
        "volumeNumber": "8"
      }
    ], 
    "name": "Glutamine synthetase is necessary for sarcoma adaptation to glutamine deprivation and tumor growth", 
    "pagination": "20", 
    "productId": [
      {
        "name": "readcube_id", 
        "type": "PropertyValue", 
        "value": [
          "06ca943515286083eb2e9021ab6b83de5b38f01e4ae2390dfe65536693b9385c"
        ]
      }, 
      {
        "name": "pubmed_id", 
        "type": "PropertyValue", 
        "value": [
          "30808861"
        ]
      }, 
      {
        "name": "nlm_unique_id", 
        "type": "PropertyValue", 
        "value": [
          "101580004"
        ]
      }, 
      {
        "name": "doi", 
        "type": "PropertyValue", 
        "value": [
          "10.1038/s41389-019-0129-z"
        ]
      }, 
      {
        "name": "dimensions_id", 
        "type": "PropertyValue", 
        "value": [
          "pub.1112387989"
        ]
      }
    ], 
    "sameAs": [
      "https://doi.org/10.1038/s41389-019-0129-z", 
      "https://app.dimensions.ai/details/publication/pub.1112387989"
    ], 
    "sdDataset": "articles", 
    "sdDatePublished": "2019-04-11T11:19", 
    "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/v90/0000000354_0000000354/records_11713_00000002.jsonl", 
    "type": "ScholarlyArticle", 
    "url": "https://www.nature.com/articles/s41389-019-0129-z"
  }
]
 

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/s41389-019-0129-z'

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/s41389-019-0129-z'

Turtle is a human-readable linked data format.

curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1038/s41389-019-0129-z'

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

curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1038/s41389-019-0129-z'


 

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

222 TRIPLES      21 PREDICATES      69 URIs      21 LITERALS      9 BLANK NODES

Subject Predicate Object
1 sg:pub.10.1038/s41389-019-0129-z schema:about anzsrc-for:06
2 anzsrc-for:0601
3 schema:author N20cbdc80c8f84dffab1116fd0a255f15
4 schema:citation sg:pub.10.1007/s00259-002-0859-5
5 sg:pub.10.1038/bjc.2014.425
6 sg:pub.10.1038/ncb3272
7 sg:pub.10.1038/ncomms11457
8 sg:pub.10.1038/nrc.2016.71
9 sg:pub.10.1038/nrc1168
10 sg:pub.10.1038/nrc3087
11 sg:pub.10.1038/nrd3504
12 sg:pub.10.1186/2045-3329-2-14
13 https://doi.org/10.1016/j.cancergen.2016.03.004
14 https://doi.org/10.1016/j.cell.2011.02.013
15 https://doi.org/10.1016/j.celrep.2017.07.054
16 https://doi.org/10.1016/j.cmet.2007.10.002
17 https://doi.org/10.1016/j.cmet.2015.09.025
18 https://doi.org/10.1016/j.cmet.2016.01.007
19 https://doi.org/10.1016/j.ijrobp.2014.08.005
20 https://doi.org/10.1016/j.molcel.2016.02.032
21 https://doi.org/10.1016/j.pharmthera.2012.10.004
22 https://doi.org/10.1016/j.tcb.2017.11.006
23 https://doi.org/10.1016/s0167-4838(99)00270-8
24 https://doi.org/10.1053/j.semnuclmed.2016.12.004
25 https://doi.org/10.1080/14728222.2017.1303484
26 https://doi.org/10.1097/rlu.0b013e318217ae2e
27 https://doi.org/10.1101/cshperspect.a025650
28 https://doi.org/10.1126/science.1160809
29 https://doi.org/10.1155/2011/756982
30 https://doi.org/10.1158/1078-0432.ccr-13-0633
31 https://doi.org/10.1158/1078-0432.ccr-17-1121
32 https://doi.org/10.1172/jci69600
33 https://doi.org/10.1200/jco.2005.01.7079
34 https://doi.org/10.12688/f1000research.8631.1
35 https://doi.org/10.14694/edbk_175378
36 https://doi.org/10.1615/critrevoncog.2015013553
37 https://doi.org/10.1615/critrevoncog.2015013800
38 https://doi.org/10.2174/138955708785132800
39 https://doi.org/10.3389/fonc.2015.00190
40 https://doi.org/10.3390/genes9020108
41 https://doi.org/10.4155/fmc.13.130
42 https://doi.org/10.4161/cc.28010
43 https://doi.org/10.4161/cc.7.2.5229
44 schema:datePublished 2019-03
45 schema:datePublishedReg 2019-03-01
46 schema:description Despite a growing body of knowledge about the genomic landscape and molecular pathogenesis of sarcomas, translation of basic discoveries into targeted therapies and significant clinical gains has remained elusive. Renewed interest in altered metabolic properties of cancer cells has led to an exploration of targeting metabolic dependencies as a novel therapeutic strategy. In this study, we have characterized the dependency of human pediatric sarcoma cells on key metabolic substrates and identified a mechanism of adaptation to metabolic stress by examining proliferation and bioenergetic properties of rhabdomyosarcoma and Ewing sarcoma cells under varying concentrations of glucose and glutamine. While all cell lines tested were completely growth-inhibited by lack of glucose, cells adapted to glutamine deprivation, and restored proliferation following an initial period of reduced growth. We show that expression of glutamine synthetase (GS), the enzyme responsible for de novo glutamine synthesis, increased during glutamine deprivation, and that pharmacological or shRNA-mediated GS inhibition abolished proliferation of glutamine-deprived cells, while having no effect on cells grown under normal culture conditions. Moreover, the GS substrates and glutamine precursors glutamate and ammonia restored proliferation of glutamine-deprived cells in a GS-dependent manner, further emphasizing the necessity of GS for adaptation to glutamine stress. Furthermore, pharmacological and shRNA-mediated GS inhibition significantly reduced orthotopic xenograft tumor growth. We also show that glutamine supports sarcoma nucleotide biosynthesis and optimal mitochondrial bioenergetics. Our findings demonstrate that GS mediates proliferation of glutamine-deprived pediatric sarcomas, and suggest that targeting metabolic dependencies of sarcomas should be further investigated as a potential therapeutic strategy.
47 schema:genre research_article
48 schema:inLanguage en
49 schema:isAccessibleForFree false
50 schema:isPartOf Ne2aef290446b4e8bb944164935976ee6
51 Nf3d0bf8f548e4fccb6894684393d8741
52 sg:journal.1046557
53 schema:name Glutamine synthetase is necessary for sarcoma adaptation to glutamine deprivation and tumor growth
54 schema:pagination 20
55 schema:productId N4d30cbdd3bd346209fc76f301b63c037
56 N67532955e9ed4091bbf2e7477e2d8a73
57 N96ff7296a2974b7ca85fbf08471bdbc3
58 Nb7062efe958b470cae77b75537d745db
59 Nc2a630b5c9344ed2bb0c0f60cb541a89
60 schema:sameAs https://app.dimensions.ai/details/publication/pub.1112387989
61 https://doi.org/10.1038/s41389-019-0129-z
62 schema:sdDatePublished 2019-04-11T11:19
63 schema:sdLicense https://scigraph.springernature.com/explorer/license/
64 schema:sdPublisher N90390166b0ef43bd82b8fecde4b8704e
65 schema:url https://www.nature.com/articles/s41389-019-0129-z
66 sgo:license sg:explorer/license/
67 sgo:sdDataset articles
68 rdf:type schema:ScholarlyArticle
69 N0724ed572b2a4a64bd1bb671b46ec4c9 rdf:first Nfd3dc969c5e5412498266e35244537fb
70 rdf:rest rdf:nil
71 N0bab0191bbf24550a423e1c6956434c9 schema:affiliation https://www.grid.ac/institutes/grid.417768.b
72 schema:familyName Mendoza
73 schema:givenName Arnulfo
74 rdf:type schema:Person
75 N0c40ce3119eb481ca8a7f82e4a324629 schema:affiliation https://www.grid.ac/institutes/grid.417768.b
76 schema:familyName Issaq
77 schema:givenName Sameer H.
78 rdf:type schema:Person
79 N20cbdc80c8f84dffab1116fd0a255f15 rdf:first N0c40ce3119eb481ca8a7f82e4a324629
80 rdf:rest N34a6d26f63af44139b26bb026c2538c1
81 N2544bb34b4c14830b303f72ff89e5f4c rdf:first N9890e9627b15489289e5e75e5a65de04
82 rdf:rest N0724ed572b2a4a64bd1bb671b46ec4c9
83 N34a6d26f63af44139b26bb026c2538c1 rdf:first N0bab0191bbf24550a423e1c6956434c9
84 rdf:rest N2544bb34b4c14830b303f72ff89e5f4c
85 N4d30cbdd3bd346209fc76f301b63c037 schema:name readcube_id
86 schema:value 06ca943515286083eb2e9021ab6b83de5b38f01e4ae2390dfe65536693b9385c
87 rdf:type schema:PropertyValue
88 N67532955e9ed4091bbf2e7477e2d8a73 schema:name dimensions_id
89 schema:value pub.1112387989
90 rdf:type schema:PropertyValue
91 N90390166b0ef43bd82b8fecde4b8704e schema:name Springer Nature - SN SciGraph project
92 rdf:type schema:Organization
93 N96ff7296a2974b7ca85fbf08471bdbc3 schema:name doi
94 schema:value 10.1038/s41389-019-0129-z
95 rdf:type schema:PropertyValue
96 N9890e9627b15489289e5e75e5a65de04 schema:affiliation https://www.grid.ac/institutes/grid.418021.e
97 schema:familyName Fox
98 schema:givenName Stephen D.
99 rdf:type schema:Person
100 Nb7062efe958b470cae77b75537d745db schema:name nlm_unique_id
101 schema:value 101580004
102 rdf:type schema:PropertyValue
103 Nc2a630b5c9344ed2bb0c0f60cb541a89 schema:name pubmed_id
104 schema:value 30808861
105 rdf:type schema:PropertyValue
106 Ne2aef290446b4e8bb944164935976ee6 schema:volumeNumber 8
107 rdf:type schema:PublicationVolume
108 Nf3d0bf8f548e4fccb6894684393d8741 schema:issueNumber 3
109 rdf:type schema:PublicationIssue
110 Nfd3dc969c5e5412498266e35244537fb schema:affiliation https://www.grid.ac/institutes/grid.239546.f
111 schema:familyName Helman
112 schema:givenName Lee J.
113 rdf:type schema:Person
114 anzsrc-for:06 schema:inDefinedTermSet anzsrc-for:
115 schema:name Biological Sciences
116 rdf:type schema:DefinedTerm
117 anzsrc-for:0601 schema:inDefinedTermSet anzsrc-for:
118 schema:name Biochemistry and Cell Biology
119 rdf:type schema:DefinedTerm
120 sg:journal.1046557 schema:issn 2157-9024
121 schema:name Oncogenesis
122 rdf:type schema:Periodical
123 sg:pub.10.1007/s00259-002-0859-5 schema:sameAs https://app.dimensions.ai/details/publication/pub.1049393085
124 https://doi.org/10.1007/s00259-002-0859-5
125 rdf:type schema:CreativeWork
126 sg:pub.10.1038/bjc.2014.425 schema:sameAs https://app.dimensions.ai/details/publication/pub.1005692217
127 https://doi.org/10.1038/bjc.2014.425
128 rdf:type schema:CreativeWork
129 sg:pub.10.1038/ncb3272 schema:sameAs https://app.dimensions.ai/details/publication/pub.1032287924
130 https://doi.org/10.1038/ncb3272
131 rdf:type schema:CreativeWork
132 sg:pub.10.1038/ncomms11457 schema:sameAs https://app.dimensions.ai/details/publication/pub.1021043408
133 https://doi.org/10.1038/ncomms11457
134 rdf:type schema:CreativeWork
135 sg:pub.10.1038/nrc.2016.71 schema:sameAs https://app.dimensions.ai/details/publication/pub.1045229038
136 https://doi.org/10.1038/nrc.2016.71
137 rdf:type schema:CreativeWork
138 sg:pub.10.1038/nrc1168 schema:sameAs https://app.dimensions.ai/details/publication/pub.1006265436
139 https://doi.org/10.1038/nrc1168
140 rdf:type schema:CreativeWork
141 sg:pub.10.1038/nrc3087 schema:sameAs https://app.dimensions.ai/details/publication/pub.1026938278
142 https://doi.org/10.1038/nrc3087
143 rdf:type schema:CreativeWork
144 sg:pub.10.1038/nrd3504 schema:sameAs https://app.dimensions.ai/details/publication/pub.1028324544
145 https://doi.org/10.1038/nrd3504
146 rdf:type schema:CreativeWork
147 sg:pub.10.1186/2045-3329-2-14 schema:sameAs https://app.dimensions.ai/details/publication/pub.1021871767
148 https://doi.org/10.1186/2045-3329-2-14
149 rdf:type schema:CreativeWork
150 https://doi.org/10.1016/j.cancergen.2016.03.004 schema:sameAs https://app.dimensions.ai/details/publication/pub.1031932079
151 rdf:type schema:CreativeWork
152 https://doi.org/10.1016/j.cell.2011.02.013 schema:sameAs https://app.dimensions.ai/details/publication/pub.1023540354
153 rdf:type schema:CreativeWork
154 https://doi.org/10.1016/j.celrep.2017.07.054 schema:sameAs https://app.dimensions.ai/details/publication/pub.1091215778
155 rdf:type schema:CreativeWork
156 https://doi.org/10.1016/j.cmet.2007.10.002 schema:sameAs https://app.dimensions.ai/details/publication/pub.1006428882
157 rdf:type schema:CreativeWork
158 https://doi.org/10.1016/j.cmet.2015.09.025 schema:sameAs https://app.dimensions.ai/details/publication/pub.1053690973
159 rdf:type schema:CreativeWork
160 https://doi.org/10.1016/j.cmet.2016.01.007 schema:sameAs https://app.dimensions.ai/details/publication/pub.1039310213
161 rdf:type schema:CreativeWork
162 https://doi.org/10.1016/j.ijrobp.2014.08.005 schema:sameAs https://app.dimensions.ai/details/publication/pub.1003649526
163 rdf:type schema:CreativeWork
164 https://doi.org/10.1016/j.molcel.2016.02.032 schema:sameAs https://app.dimensions.ai/details/publication/pub.1006778665
165 rdf:type schema:CreativeWork
166 https://doi.org/10.1016/j.pharmthera.2012.10.004 schema:sameAs https://app.dimensions.ai/details/publication/pub.1029630083
167 rdf:type schema:CreativeWork
168 https://doi.org/10.1016/j.tcb.2017.11.006 schema:sameAs https://app.dimensions.ai/details/publication/pub.1099623945
169 rdf:type schema:CreativeWork
170 https://doi.org/10.1016/s0167-4838(99)00270-8 schema:sameAs https://app.dimensions.ai/details/publication/pub.1044614628
171 rdf:type schema:CreativeWork
172 https://doi.org/10.1053/j.semnuclmed.2016.12.004 schema:sameAs https://app.dimensions.ai/details/publication/pub.1045863211
173 rdf:type schema:CreativeWork
174 https://doi.org/10.1080/14728222.2017.1303484 schema:sameAs https://app.dimensions.ai/details/publication/pub.1084165971
175 rdf:type schema:CreativeWork
176 https://doi.org/10.1097/rlu.0b013e318217ae2e schema:sameAs https://app.dimensions.ai/details/publication/pub.1024829111
177 rdf:type schema:CreativeWork
178 https://doi.org/10.1101/cshperspect.a025650 schema:sameAs https://app.dimensions.ai/details/publication/pub.1033606975
179 rdf:type schema:CreativeWork
180 https://doi.org/10.1126/science.1160809 schema:sameAs https://app.dimensions.ai/details/publication/pub.1033271739
181 rdf:type schema:CreativeWork
182 https://doi.org/10.1155/2011/756982 schema:sameAs https://app.dimensions.ai/details/publication/pub.1052527823
183 rdf:type schema:CreativeWork
184 https://doi.org/10.1158/1078-0432.ccr-13-0633 schema:sameAs https://app.dimensions.ai/details/publication/pub.1037622162
185 rdf:type schema:CreativeWork
186 https://doi.org/10.1158/1078-0432.ccr-17-1121 schema:sameAs https://app.dimensions.ai/details/publication/pub.1091621417
187 rdf:type schema:CreativeWork
188 https://doi.org/10.1172/jci69600 schema:sameAs https://app.dimensions.ai/details/publication/pub.1036293561
189 rdf:type schema:CreativeWork
190 https://doi.org/10.1200/jco.2005.01.7079 schema:sameAs https://app.dimensions.ai/details/publication/pub.1026327123
191 rdf:type schema:CreativeWork
192 https://doi.org/10.12688/f1000research.8631.1 schema:sameAs https://app.dimensions.ai/details/publication/pub.1027022849
193 rdf:type schema:CreativeWork
194 https://doi.org/10.14694/edbk_175378 schema:sameAs https://app.dimensions.ai/details/publication/pub.1085765647
195 rdf:type schema:CreativeWork
196 https://doi.org/10.1615/critrevoncog.2015013553 schema:sameAs https://app.dimensions.ai/details/publication/pub.1068132376
197 rdf:type schema:CreativeWork
198 https://doi.org/10.1615/critrevoncog.2015013800 schema:sameAs https://app.dimensions.ai/details/publication/pub.1068132382
199 rdf:type schema:CreativeWork
200 https://doi.org/10.2174/138955708785132800 schema:sameAs https://app.dimensions.ai/details/publication/pub.1069182928
201 rdf:type schema:CreativeWork
202 https://doi.org/10.3389/fonc.2015.00190 schema:sameAs https://app.dimensions.ai/details/publication/pub.1001649918
203 rdf:type schema:CreativeWork
204 https://doi.org/10.3390/genes9020108 schema:sameAs https://app.dimensions.ai/details/publication/pub.1101125257
205 rdf:type schema:CreativeWork
206 https://doi.org/10.4155/fmc.13.130 schema:sameAs https://app.dimensions.ai/details/publication/pub.1029120446
207 rdf:type schema:CreativeWork
208 https://doi.org/10.4161/cc.28010 schema:sameAs https://app.dimensions.ai/details/publication/pub.1072297547
209 rdf:type schema:CreativeWork
210 https://doi.org/10.4161/cc.7.2.5229 schema:sameAs https://app.dimensions.ai/details/publication/pub.1072299672
211 rdf:type schema:CreativeWork
212 https://www.grid.ac/institutes/grid.239546.f schema:alternateName Children's Hospital of Los Angeles
213 schema:name Children’s Center for Cancer and Blood Diseases, Children’s Hospital Los Angeles, Los Angeles, CA, USA
214 Departments of Pediatrics and Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
215 Pediatric Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
216 rdf:type schema:Organization
217 https://www.grid.ac/institutes/grid.417768.b schema:alternateName Center for Cancer Research
218 schema:name Pediatric Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
219 rdf:type schema:Organization
220 https://www.grid.ac/institutes/grid.418021.e schema:alternateName Frederick National Laboratory for Cancer Research
221 schema:name Protein Characterization Laboratory, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc., Frederick, MD, USA
222 rdf:type schema:Organization
 




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


...