Metabolic shifts toward glutamine regulate tumor growth, invasion and bioenergetics in ovarian cancer

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dc.citation.journalTitleMolecular Systems Biologyen_US
dc.citation.volumeNumber10en_US
dc.contributor.authorYang, Lifengen_US
dc.contributor.authorMoss, Tyleren_US
dc.contributor.authorMangala, Lingegowda S.en_US
dc.contributor.authorMarini, Juanen_US
dc.contributor.authorZhao, Hongyunen_US
dc.contributor.authorWahlig, Stephenen_US
dc.contributor.authorArmaiz-Pena, Guillermoen_US
dc.contributor.authorJiang, Dahaien_US
dc.contributor.authorAchreja, Abhinaven_US
dc.contributor.authorWin, Juliaen_US
dc.contributor.authorRoopaimoole, Rajeshaen_US
dc.contributor.authorRodriguez-Aguayo, Cristianen_US
dc.contributor.authorMercado-Uribe, Imeldaen_US
dc.contributor.authorLopez-Berestein, Gabrielen_US
dc.contributor.authorLiu, Jinsongen_US
dc.contributor.authorTsukamoto, Takashien_US
dc.contributor.authorSood, Anil K.en_US
dc.contributor.authorRam, Prahlad T.en_US
dc.contributor.authorNagrath, Deepaken_US
dc.contributor.orgBioengineeringen_US
dc.contributor.orgChemical and Biomolecular Engineeringen_US
dc.date.accessioned2014-10-09T15:38:25Zen_US
dc.date.available2014-10-09T15:38:25Zen_US
dc.date.issued2014en_US
dc.description.abstractGlutamine can play a critical role in cellular growth in multiple cancers. Glutamine‐addicted cancer cells are dependent on glutamine for viability, and their metabolism is reprogrammed for glutamine utilization through the tricarboxylic acid (TCA) cycle. Here, we have uncovered a missing link between cancer invasiveness and glutamine dependence. Using isotope tracer and bioenergetic analysis, we found that low‐invasive ovarian cancer (OVCA) cells are glutamine independent, whereas high‐invasive OVCA cells are markedly glutamine dependent. Consistent with our findings, OVCA patients’ microarray data suggest that glutaminolysis correlates with poor survival. Notably, the ratio of gene expression associated with glutamine anabolism versus catabolism has emerged as a novel biomarker for patient prognosis. Significantly, we found that glutamine regulates the activation of STAT3, a mediator of signaling pathways which regulates cancer hallmarks in invasive OVCA cells. Our findings suggest that a combined approach of targeting high‐invasive OVCA cells by blocking glutamine's entry into the TCA cycle, along with targeting low‐invasive OVCA cells by inhibiting glutamine synthesis and STAT3 may lead to potential therapeutic approaches for treating OVCAs.en_US
dc.identifier.citationYang, Lifeng, Moss, Tyler, Mangala, Lingegowda S., et al.. "Metabolic shifts toward glutamine regulate tumor growth, invasion and bioenergetics in ovarian cancer." <i>Molecular Systems Biology,</i> 10, (2014) EMBO: http://dx.doi.org/10.1002/msb.20134892.en_US
dc.identifier.doihttp://dx.doi.org/10.1002/msb.20134892en_US
dc.identifier.urihttps://hdl.handle.net/1911/77505en_US
dc.language.isoengen_US
dc.publisherEMBOen_US
dc.rightsThis is an open access article under the terms of the Creative Commons Attribution 4.0 License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.en_US
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en_US
dc.subject.keywordcancer metabolismen_US
dc.subject.keywordglutamine dependenceen_US
dc.subject.keywordglutaminolysisen_US
dc.subject.keywordinvasionen_US
dc.subject.keywordovarian canceren_US
dc.titleMetabolic shifts toward glutamine regulate tumor growth, invasion and bioenergetics in ovarian canceren_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
dc.type.publicationpublisher versionen_US
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