Amplification of USP13 drives ovarian cancer metabolism

Cecil Han, Lifeng Yang, Hyun Ho Choi, Joelle Baddour, Abhinav Achreja, Yunhua Liu, Yujing Li, Jiada Li, Guohui Wan, Cheng Huang, Guang Ji, Xinna Zhang, Deepak Nagrath () and Xiongbin Lu ()
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Cecil Han: The University of Texas MD Anderson Cancer Center
Lifeng Yang: Rice University
Hyun Ho Choi: The University of Texas MD Anderson Cancer Center
Joelle Baddour: Rice University
Abhinav Achreja: Rice University
Yunhua Liu: The University of Texas MD Anderson Cancer Center
Yujing Li: The University of Texas MD Anderson Cancer Center
Jiada Li: The State Key Laboratory of Medical Genetics and School of Life Sciences, Central South University
Guohui Wan: The University of Texas MD Anderson Cancer Center
Cheng Huang: Drug Discovery Laboratory, School of Pharmacy, Shanghai University of Traditional Chinese Medicine
Guang Ji: Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine
Xinna Zhang: The University of Texas MD Anderson Cancer Center
Deepak Nagrath: Rice University
Xiongbin Lu: The University of Texas MD Anderson Cancer Center

Nature Communications, 2016, vol. 7, issue 1, 1-16

Abstract: 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.

Date: 2016
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DOI: 10.1038/ncomms13525

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