Skip to main content
Advertisement
  • Other Publications
    • EMBO Press
    • EMBO reports (Home)
    • The EMBO Journal
    • EMBO Molecular Medicine
    • Molecular Systems Biology
    • Life Science Alliance
Login

   

Search

Advanced Search

Journal

  • Home
  • Latest Online
  • Current Issue
  • Archive
  • Subject Collections
  • Review Series & Focuses

Authors & Referees

  • Submit
  • Author Guidelines
  • Aims & Scope
  • Editors & Board
  • Transparent Process
  • Bibliometrics
  • Referee Guidelines
  • Open Access

Info

  • E-Mail Editorial Office
  • Alerts
  • RSS Feeds
  • Subscriptions & Access
  • Reprints & Permissions
  • Advertise & Sponsor
  • Media Partners
  • News & Press
  • Recommend to Librarian
  • Customer Service
  • Home
  • Latest Online

Transparent Process

Scientific Report

Glutamine‐utilizing transaminases are a metabolic vulnerability of TAZ/YAP‐activated cancer cells

Chih‐Sheng Yang, Eleni Stampouloglou, Nathan M Kingston, Liye Zhang, Stefano Monti, View ORCID ProfileXaralabos Varelas
DOI 10.15252/embr.201643577 | Published online 16.04.2018
EMBO reports (2018) e43577
Chih‐Sheng Yang
Department of Biochemistry, Boston University School of Medicine, Boston, MA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Eleni Stampouloglou
Department of Biochemistry, Boston University School of Medicine, Boston, MA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Nathan M Kingston
Department of Biochemistry, Boston University School of Medicine, Boston, MA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Liye Zhang
Section of Computational Biomedicine, Department of Medicine, Boston University School of Medicine, Boston, MA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Stefano Monti
Section of Computational Biomedicine, Department of Medicine, Boston University School of Medicine, Boston, MA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Xaralabos Varelas
Department of Biochemistry, Boston University School of Medicine, Boston, MA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site

Author Affiliations

  1. Chih‐Sheng Yang1,†,
  2. Eleni Stampouloglou1,†,
  3. Nathan M Kingston1,†,
  4. Liye Zhang2,3,
  5. Stefano Monti2 and
  6. Xaralabos Varelas (xvarelas{at}bu.edu)*,1
  1. 1Department of Biochemistry, Boston University School of Medicine, Boston, MA, USA
  2. 2Section of Computational Biomedicine, Department of Medicine, Boston University School of Medicine, Boston, MA, USA
  3. 3Present Address: School of Life Science and Technology, ShanghaiTech University, Shanghai, China
  1. ↵*Corresponding author. Tel: +1 617 358 4575; E‐mail: xvarelas{at}bu.edu
  1. ↵† These authors contributed equally to this work

View Abstract
  • Article
  • Figures & Data
  • Transparent Process
Loading

Abstract

The transcriptional regulators TAZ and YAP (TAZ/YAP) have emerged as pro‐tumorigenic factors that drive many oncogenic traits, including induction of cell growth, resistance to cell death, and activation of processes that promote migration and invasion. Here, we report that TAZ/YAP reprogram cellular energetics to promote the dependence of breast cancer cell growth on exogenous glutamine. Rescue experiments with glutamine‐derived metabolites suggest an essential role for glutamate and α‐ketoglutarate (AKG) in TAZ/YAP‐driven cell growth in the absence of glutamine. Analysis of enzymes that mediate the conversion of glutamate to AKG shows that TAZ/YAP induce glutamic–oxaloacetic transaminase (GOT1) and phosphoserine aminotransferase (PSAT1) expression and that TAZ/YAP activity positively correlates with transaminase expression in breast cancer patients. Notably, we find that the transaminase inhibitor aminooxyacetate (AOA) represses cell growth in a TAZ/YAP‐dependent manner, identifying transamination as a potential vulnerable metabolic requirement for TAZ/YAP‐driven breast cancer.

Synopsis

Embedded Image

Elevated levels of the transcriptional regulators TAZ/YAP, key effectors of Hippo pathway signalling, mediate breast cancer cell growth dependence on exogenous glutamine. Cancer cells with high TAZ/YAP activity are sensitive to transaminase inhibition.

  • High TAZ/YAP levels alter cellular energetics to promote breast cancer cell growth dependence on exogenous glutamine.

  • TAZ/YAP promote the expression of glutamic–oxaloacetic transaminase (GOT1) and phosphoserine aminotransferase (PSAT1).

  • Transaminase inhibition represses breast cancer cell growth in a TAZ/YAP dependent manner.

  • breast cancer
  • cellular metabolism
  • glutamine
  • Hippo
  • Transaminase

EMBO Reports (2018) e43577

  • Received October 26, 2016.
  • Revision received March 19, 2018.
  • Accepted March 23, 2018.
  • © 2018 The Authors
View Full Text

Subscribers, please sign in with your username and password.

Log in using your username and password

Enter your EMBO Reports username.
Enter the password that accompanies your username.
Forgot your user name or password?

Log in through your institution

You may be able to gain access using your login credentials for your institution. Contact your library if you do not have a username and password.
If your organization uses OpenAthens, you can log in using your OpenAthens username and password. To check if your institution is supported, please see this list. Contact your library for more details.

Pay Per Article - You may access this article (from the computer you are currently using) for 1 day for US$35.00

Regain Access - You can regain access to a recent Pay per Article purchase if your access period has not yet expired.

EMBO Members please login here to access the journals

Subscribe to the Journal

EMBO Journal

EMBO Reports

Recommend to your Librarian

EMBO Journal

EMBO Reports

 

 

Previous Article in this IssueNext Article in this Issue
Back to top

  • PDF
  • Share
  • Export
  • Print
Loading

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
In this Issue
Volume 19, Issue 4
01 April 2018 | pp -
EMBO reports: 19 (4)
About the cover
Alert me when this article is cited
Alert me if a correction is posted

Article

  • Article
    • Abstract
    • Synopsis
    • Introduction
    • Results and Discussion
    • Materials and Methods
    • Author contributions
    • Conflict of interest
    • Expanded View
    • Acknowledgements
    • References
  • Figures & Data
  • Transparent Process

Related Content

More Scientific Reports

  • PRDM4 mediates YAP‐induced cell invasion by activating leukocyte‐specific integrin β2 expression
    Huan Liu, Xiaoming Dai, Xiaolei Cao, Huan Yan, Xinyan Ji, Haitao Zhang, Shuying Shen, Yuan Si, Hailong Zhang, Jianfeng Chen, Li Li, Jonathan C Zhao, Jindan Yu, Xin‐Hua Feng, Bin Zhao
    EMBO reports : e45180
  • Disentangling the molecular determinants for Cenp‐F localization to nuclear pores and kinetochores
    Alessandro Berto, Jinchao Yu, Stéphanie Morchoisne‐Bolhy, Chiara Bertipaglia, Richard Vallee, Julien Dumont, Francoise Ochsenbein, Raphael Guerois, Valérie Doye
    EMBO reports : e44742
More Scientific Report

Related Articles

Cited By...

Request Permissions

Subject Areas

  • Cancer
  • Metabolism
  • Post-translational Modifications, Proteolysis & Proteomics

Journal

  • Latest Online
  • Current Issue
  • Archive
  • Bibliometrics
  • E-Mail Editorial Office

Authors & References

  • Aims & Scope
  • Editors & Board
  • Transparent Process
  • Author Guidelines
  • Referee Guidelines
  • Open Access
  • Submit

Info

  • Alerts
  • RSS Feeds
  • Subscriptions & Access
  • Reprints & Permissions
  • Advertise & Sponsor
  • News & Press
  • Recommend to Librarian
  • Customer Service

EMBO

  • Funding & Awards
  • Events
  • Science Policy
  • Members
  • About EMBO

Online ISSN  1469-3178

Copyright© 2018 EMBO

This website is best viewed using the latest versions of all modern web browsers. Older browsers may not display correctly.