Amplification of USP13 drives ovarian cancer metabolism

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dc.citation.articleNumber13525en_US
dc.citation.journalTitleNature Communicationsen_US
dc.citation.volumeNumber7en_US
dc.contributor.authorHan, Cecilen_US
dc.contributor.authorYang, Lifengen_US
dc.contributor.authorChoi, Hyun Hoen_US
dc.contributor.authorBaddour, Joelleen_US
dc.contributor.authorAchreja, Abhinaven_US
dc.contributor.authorLiu, Yunhuaen_US
dc.contributor.authorLi, Yujingen_US
dc.contributor.authorLi, Jiadaen_US
dc.contributor.authorWan, Guohuien_US
dc.contributor.authorHuang, Chengen_US
dc.contributor.authorJi, Guangen_US
dc.contributor.authorZhang, Xinnaen_US
dc.contributor.authorNagrath, Deepaken_US
dc.contributor.authorLu, Xiongbinen_US
dc.date.accessioned2017-01-30T17:29:31Zen_US
dc.date.available2017-01-30T17:29:31Zen_US
dc.date.issued2016en_US
dc.description.abstractDysregulated energetic metabolism has been recently identified as a hallmark of cancer. Although mutations in metabolic enzymes hardwire metabolism to tumourigenesis, they are relatively infrequent in ovarian cancer. More often, cancer metabolism is re-engineered by altered abundance and activity of the metabolic enzymes. Here we identify ubiquitin-specific peptidase 13 (USP13) as a master regulator that drives ovarian cancer metabolism. USP13 specifically deubiquitinates and thus upregulates ATP citrate lyase and oxoglutarate dehydrogenase, two key enzymes that determine mitochondrial respiration, glutaminolysis and fatty acid synthesis. The USP13 gene is co-amplified with PIK3CA in 29.3% of high-grade serous ovarian cancers and its overexpression is significantly associated with poor clinical outcome. Inhibiting USP13 remarkably suppresses ovarian tumour progression and sensitizes tumour cells to the treatment of PI3K/AKT inhibitor. Our results reveal an important metabolism-centric role of USP13, which may lead to potential therapeutics targeting USP13 in ovarian cancers.en_US
dc.identifier.citationHan, Cecil, Yang, Lifeng, Choi, Hyun Ho, et al.. "Amplification of USP13 drives ovarian cancer metabolism." <i>Nature Communications,</i> 7, (2016) Springer Nature: http://dx.doi.org/10.1038/ncomms13525.en_US
dc.identifier.doihttp://dx.doi.org/10.1038/ncomms13525en_US
dc.identifier.urihttps://hdl.handle.net/1911/93815en_US
dc.language.isoengen_US
dc.publisherSpringer Natureen_US
dc.rightsThis work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material.en_US
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en_US
dc.titleAmplification of USP13 drives ovarian cancer metabolismen_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
dc.type.publicationpublisher versionen_US
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