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

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dc.citation.journalTitleMolecular Systems Biology
dc.citation.volumeNumber10
dc.contributor.authorYang, Lifeng
dc.contributor.authorMoss, Tyler
dc.contributor.authorMangala, Lingegowda S.
dc.contributor.authorMarini, Juan
dc.contributor.authorZhao, Hongyun
dc.contributor.authorWahlig, Stephen
dc.contributor.authorArmaiz-Pena, Guillermo
dc.contributor.authorJiang, Dahai
dc.contributor.authorAchreja, Abhinav
dc.contributor.authorWin, Julia
dc.contributor.authorRoopaimoole, Rajesha
dc.contributor.authorRodriguez-Aguayo, Cristian
dc.contributor.authorMercado-Uribe, Imelda
dc.contributor.authorLopez-Berestein, Gabriel
dc.contributor.authorLiu, Jinsong
dc.contributor.authorTsukamoto, Takashi
dc.contributor.authorSood, Anil K.
dc.contributor.authorRam, Prahlad T.
dc.contributor.authorNagrath, Deepak
dc.date.accessioned2014-10-09T15:38:25Z
dc.date.available2014-10-09T15:38:25Z
dc.date.issued2014
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.
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.
dc.identifier.doihttp://dx.doi.org/10.1002/msb.20134892
dc.identifier.urihttps://hdl.handle.net/1911/77505
dc.language.isoeng
dc.publisherEMBO
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.
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subject.keywordcancer metabolism
dc.subject.keywordglutamine dependence
dc.subject.keywordglutaminolysis
dc.subject.keywordinvasion
dc.subject.keywordovarian cancer
dc.titleMetabolic shifts toward glutamine regulate tumor growth, invasion and bioenergetics in ovarian cancer
dc.typeJournal article
dc.type.dcmiText
dc.type.publicationpublisher version
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