Amplification of USP13 drives ovarian cancer metabolism

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Author
Han, Cecil
Yang, Lifeng
Choi, Hyun Ho
Baddour, Joelle
Achreja, Abhinav
Liu, Yunhua
Li, Yujing
Li, Jiada
Wan, Guohui
Huang, Cheng
Ji, Guang
Zhang, Xinna
Nagrath, Deepak
Lu, Xiongbin
Date
2016
Abstract
Dysregulated 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.
Citation
Han, Cecil, Yang, Lifeng, Choi, Hyun Ho, et al.. "Amplification of USP13 drives ovarian cancer metabolism." Nature Communications, 7, (2016) Springer Nature: http://dx.doi.org/10.1038/ncomms13525.
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Journal article
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Springer Nature
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https://hdl.handle.net/1911/93815
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This 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.
Except where otherwise noted, this item's license is described as This 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.