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dc.contributor.authorYang, Lifeng
Moss, Tyler
Mangala, Lingegowda S.
Marini, Juan
Zhao, Hongyun
Wahlig, Stephen
Armaiz-Pena, Guillermo
Jiang, Dahai
Achreja, Abhinav
Win, Julia
Roopaimoole, Rajesha
Rodriguez-Aguayo, Cristian
Mercado-Uribe, Imelda
Lopez-Berestein, Gabriel
Liu, Jinsong
Tsukamoto, Takashi
Sood, Anil K.
Ram, Prahlad T.
Nagrath, Deepak
dc.date.accessioned 2014-10-09T15:38:25Z
dc.date.available 2014-10-09T15:38:25Z
dc.date.issued 2014
dc.identifier.citation Yang, Lifeng, Moss, Tyler, Mangala, Lingegowda S., et al.. "Metabolic shifts toward glutamine regulate tumor growth, invasion and bioenergetics in ovarian cancer." Molecular Systems Biology, 10, (2014) EMBO: http://dx.doi.org/10.1002/msb.20134892.
dc.identifier.urihttps://hdl.handle.net/1911/77505
dc.description.abstract Glutamine 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.language.iso eng
dc.publisher EMBO
dc.rights This 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.title Metabolic shifts toward glutamine regulate tumor growth, invasion and bioenergetics in ovarian cancer
dc.type Journal article
dc.contributor.funder National Institutes of Health
dc.contributor.funder Cancer Prevention and Research Institute of Texas
dc.contributor.funder Ovarian Cancer Research Fund, Inc.
dc.contributor.funder Gilder Foundation| Betty Anne Asche Murray Distinguished Professorship
dc.citation.journalTitle Molecular Systems Biology
dc.subject.keywordcancer metabolism
glutamine dependence
glutaminolysis
invasion
ovarian cancer
dc.citation.volumeNumber 10
dc.type.dcmi Text
dc.identifier.doihttp://dx.doi.org/10.1002/msb.20134892
dc.identifier.pmcid PMC4188042
dc.identifier.pmid 24799285
dc.identifier.grantID CA016672 (National Institutes of Health)
dc.identifier.grantID P50 CA083639 (National Institutes of Health)
dc.identifier.grantID P50 CA098258 (National Institutes of Health)
dc.identifier.grantID U54 CA151668 (National Institutes of Health)
dc.identifier.grantID UH2 TR000943-01 (National Institutes of Health)
dc.identifier.grantID RP110595 (Cancer Prevention and Research Institute of Texas )
dc.identifier.grantID Program Project Development Grant (Ovarian Cancer Research Fund, Inc.)
dc.identifier.grantID R21NS074151 (National Institutes of Health)
dc.type.publication publisher version


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