Amplification of USP13 drives ovarian cancer metabolism View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2016-11-28

AUTHORS

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, Xiongbin Lu

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. More... »

PAGES

13525

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/ncomms13525

DOI

http://dx.doi.org/10.1038/ncomms13525

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1053287748

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/27892457


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