Cargando…

Amplification of USP13 drives ovarian cancer metabolism

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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5133706/
https://www.ncbi.nlm.nih.gov/pubmed/27892457
http://dx.doi.org/10.1038/ncomms13525
_version_ 1782471320336859136
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
author_facet 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
author_sort Han, Cecil
collection PubMed
description 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.
format Online
Article
Text
id pubmed-5133706
institution National Center for Biotechnology Information
language English
publishDate 2016
publisher Nature Publishing Group
record_format MEDLINE/PubMed
spelling pubmed-51337062016-12-21 Amplification of USP13 drives ovarian cancer metabolism 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 Nat Commun Article 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. Nature Publishing Group 2016-11-28 /pmc/articles/PMC5133706/ /pubmed/27892457 http://dx.doi.org/10.1038/ncomms13525 Text en Copyright © 2016, The Author(s) http://creativecommons.org/licenses/by/4.0/ 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. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
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
Amplification of USP13 drives ovarian cancer metabolism
title Amplification of USP13 drives ovarian cancer metabolism
title_full Amplification of USP13 drives ovarian cancer metabolism
title_fullStr Amplification of USP13 drives ovarian cancer metabolism
title_full_unstemmed Amplification of USP13 drives ovarian cancer metabolism
title_short Amplification of USP13 drives ovarian cancer metabolism
title_sort amplification of usp13 drives ovarian cancer metabolism
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5133706/
https://www.ncbi.nlm.nih.gov/pubmed/27892457
http://dx.doi.org/10.1038/ncomms13525
work_keys_str_mv AT hancecil amplificationofusp13drivesovariancancermetabolism
AT yanglifeng amplificationofusp13drivesovariancancermetabolism
AT choihyunho amplificationofusp13drivesovariancancermetabolism
AT baddourjoelle amplificationofusp13drivesovariancancermetabolism
AT achrejaabhinav amplificationofusp13drivesovariancancermetabolism
AT liuyunhua amplificationofusp13drivesovariancancermetabolism
AT liyujing amplificationofusp13drivesovariancancermetabolism
AT lijiada amplificationofusp13drivesovariancancermetabolism
AT wanguohui amplificationofusp13drivesovariancancermetabolism
AT huangcheng amplificationofusp13drivesovariancancermetabolism
AT jiguang amplificationofusp13drivesovariancancermetabolism
AT zhangxinna amplificationofusp13drivesovariancancermetabolism
AT nagrathdeepak amplificationofusp13drivesovariancancermetabolism
AT luxiongbin amplificationofusp13drivesovariancancermetabolism