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Choline-releasing glycerophosphodiesterase EDI3 drives tumor cell migration and metastasis

  1. Stewart, Joanna D.
  2. Marchan, Rosemarie ORCID logo
  3. Lesjak, Michaela S.
  4. Lambert, Joerg ORCID logo
  5. Hergenroeder, Roland
  6. Ellis, James K.
  7. Lau, Chung-Ho
  8. Keun, Hector C.
  9. Schmitz, Gerd
  10. Schiller, Juergen
  11. Eibisch, Mandy
  12. Hedberg, Christian
  13. Waldmann, Herbert
  14. Lausch, Ekkehart
  15. Tanner, Berno
  16. Sehouli, Jalid
  17. Sagemueller, Jens
  18. Staude, Hagen
  19. Steiner, Eric
  20. Hengstler, Jan G.

WeightNameValue
1000 Titel
  • Choline-releasing glycerophosphodiesterase EDI3 drives tumor cell migration and metastasis
1000 Autor/in
  1. Stewart, Joanna D. |
  2. Marchan, Rosemarie |
  3. Lesjak, Michaela S. |
  4. Lambert, Joerg |
  5. Hergenroeder, Roland |
  6. Ellis, James K. |
  7. Lau, Chung-Ho |
  8. Keun, Hector C. |
  9. Schmitz, Gerd |
  10. Schiller, Juergen |
  11. Eibisch, Mandy |
  12. Hedberg, Christian |
  13. Waldmann, Herbert |
  14. Lausch, Ekkehart |
  15. Tanner, Berno |
  16. Sehouli, Jalid |
  17. Sagemueller, Jens |
  18. Staude, Hagen |
  19. Steiner, Eric |
  20. Hengstler, Jan G. |
1000 Erscheinungsjahr 2012
1000 LeibnizOpen
1000 Publikationstyp
  1. Artikel |
1000 Online veröffentlicht
  • 2012-05-08
1000 Erschienen in
1000 Quellenangabe
  • 109(21): 8155–8160
1000 FRL-Sammlung
1000 Verlagsversion
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3361409/?tool=pmcentrez |
  • http://doi.org/10.1073/pnas.1117654109 |
1000 Ergänzendes Material
  • http://www.pnas.org/content/109/21/8155.abstract?tab=ds |
1000 Publikationsstatus
1000 Begutachtungsstatus
1000 Sprache der Publikation
1000 Abstract/Summary
  • Metastasis from primary tumors remains a major problem for tumor therapy. In the search for markers of metastasis and more effective therapies, the tumor metabolome is relevant because of its importance to the malignant phenotype and metastatic capacity of tumor cells. Altered choline metabolism is a hallmark of cancer. More specifically, a decreased glycerophosphocholine (GPC) to phosphocholine (PC) ratio was reported in breast, ovarian, and prostate cancers. Improved strategies to exploit this altered choline metabolism are therefore required. However, the critical enzyme cleaving GPC to produce choline, the initial step in the pathway controlling the GPC/PC ratio, remained unknown. In the present work, we have identified the enzyme, here named EDI3 (endometrial differential 3). Purified recombinant EDI3 protein cleaves GPC to form glycerol-3-phosphate and choline. Silencing EDI3 in MCF-7 cells decreased this enzymatic activity, increased the intracellular GPC/PC ratio, and decreased downstream lipid metabolites. Downregulating EDI3 activity inhibited cell migration via disruption of the PKCα signaling pathway, with stable overexpression of EDI3 showing the opposite effect. EDI3 was originally identified in our screening study comparing mRNA levels in metastasizing and nonmetastasizing endometrial carcinomas. Both Kaplan–Meier and multivariate analyses revealed a negative association between high EDI3 expression and relapse-free survival time in both endometrial (P < 0.001) and ovarian (P = 0.029) cancers. Overall, we have identified EDI3, a key enzyme controlling GPC and choline metabolism. Because inhibition of EDI3 activity corrects the GPC/PC ratio and decreases the migration capacity of tumor cells, it represents a possible target for therapeutic intervention.
1000 Sacherschließung
lokal glycerophosphodiester phosphodiesterase domain containing 6
lokal glycerophosphocholine phosphodiesterase GDE1 homolog (Saccharomyces cerevisiae)
lokal lysophosphatidic acid
lokal glycerophosphodiesterase 5
lokal phosphatidic acid
1000 Fächerklassifikation (DDC)
1000 Liste der Beteiligten
  1. https://frl.publisso.de/adhoc/creator/U3Rld2FydCwgSm9hbm5hIEQu|http://orcid.org/0000-0003-4414-1633|https://frl.publisso.de/adhoc/creator/TGVzamFrLCBNaWNoYWVsYSBTLg==|http://orcid.org/0000-0003-3224-5531|https://frl.publisso.de/adhoc/creator/SGVyZ2Vucm9lZGVyLCBSb2xhbmQ=|https://frl.publisso.de/adhoc/creator/RWxsaXMsIEphbWVzIEsu|https://frl.publisso.de/adhoc/creator/TGF1LCBDaHVuZy1Ibw==|https://frl.publisso.de/adhoc/creator/S2V1biwgSGVjdG9yIEMu|https://frl.publisso.de/adhoc/creator/U2NobWl0eiwgR2VyZA==|https://frl.publisso.de/adhoc/creator/U2NoaWxsZXIsIEp1ZXJnZW4=|https://frl.publisso.de/adhoc/creator/RWliaXNjaCwgTWFuZHk=|https://frl.publisso.de/adhoc/creator/SGVkYmVyZywgQ2hyaXN0aWFu|https://frl.publisso.de/adhoc/creator/V2FsZG1hbm4sIEhlcmJlcnQ=|https://frl.publisso.de/adhoc/creator/TGF1c2NoLCBFa2tlaGFydA==|https://frl.publisso.de/adhoc/creator/VGFubmVyLCBCZXJubw==|https://frl.publisso.de/adhoc/creator/U2Vob3VsaSwgSmFsaWQ=|https://frl.publisso.de/adhoc/creator/U2FnZW11ZWxsZXIsIEplbnM=|https://frl.publisso.de/adhoc/creator/U3RhdWRlLCBIYWdlbg==|https://frl.publisso.de/adhoc/creator/U3RlaW5lciwgRXJpYw==|http://d-nb.info/gnd/175862257
1000 Label
1000 Förderer
  1. European Union |
  2. BMBF (German Federal Ministry of Education and Research) |
  3. Institute of Chemical Biology (Imperial College, London) |
1000 Fördernummer
  1. 223188; 202272; 266838
  2. -
  3. -
1000 Förderprogramm
  1. Seventh Framework Programme (FP7)-Health-Projects CancerSys; LipidomicNET; DETECTIVE
  2. OncoProfile; Virtual Liver; SysMBo
  3. -
1000 Förderung
  1. 1000 joinedFunding-child
    1000 Förderer European Union |
    1000 Förderprogramm Seventh Framework Programme (FP7)-Health-Projects CancerSys; LipidomicNET; DETECTIVE
    1000 Fördernummer 223188; 202272; 266838
  2. 1000 joinedFunding-child
    1000 Förderer BMBF (German Federal Ministry of Education and Research) |
    1000 Förderprogramm OncoProfile; Virtual Liver; SysMBo
    1000 Fördernummer -
  3. 1000 joinedFunding-child
    1000 Förderer Institute of Chemical Biology (Imperial College, London) |
    1000 Förderprogramm -
    1000 Fördernummer -
1000 Objektart article
1000 Beschrieben durch
1000 @id frl:6406487.rdf
1000 Erstellt am 2018-01-25T14:32:28.558+0100
1000 Erstellt von 22
1000 beschreibt frl:6406487
1000 Bearbeitet von 218
1000 Zuletzt bearbeitet Thu Nov 26 16:24:54 CET 2020
1000 Objekt bearb. Thu Nov 26 16:24:54 CET 2020
1000 Vgl. frl:6406487
1000 Oai Id
  1. oai:frl.publisso.de:frl:6406487 |
1000 Sichtbarkeit Metadaten public
1000 Sichtbarkeit Daten public
1000 Gegenstand von

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