UCL  IRIS
Institutional Research Information Service
UCL Logo
Please report any queries concerning the funding data grouped in the sections named "Externally Awarded" or "Internally Disbursed" (shown on the profile page) to your Research Finance Administrator. Your can find your Research Finance Administrator at https://www.ucl.ac.uk/finance/research/rs-contacts.php by entering your department
Please report any queries concerning the student data shown on the profile page to:

Email: portico-services@ucl.ac.uk

Help Desk: http://www.ucl.ac.uk/ras/portico/helpdesk
Publication Detail
The breast cancer oncogene IKKε coordinates mitochondrial function and serine metabolism
  • Publication Type:
    Journal article
  • Publication Sub Type:
    Article
  • Authors:
    Xu R, Jones W, Wilcz-Villega E, Costa ASH, Rajeeve V, Bentham RB, Bryson K, Nagano A, Yaman B, Olendo Barasa S, Wang Y, Chelala C, Cutillas P, Szabadkai G, Frezza C, Bianchi K
  • Publication date:
    11/08/2020
  • Journal:
    EMBO Reports
  • Status:
    Published
  • Print ISSN:
    1469-221X
Abstract
© 2020 The Authors. Published under the terms of the CC BY 4.0 license. IκB kinase ε (IKKε) is a key molecule at the crossroads of inflammation and cancer. Known to regulate cytokine secretion via NFκB and IRF3, the kinase is also a breast cancer oncogene, overexpressed in a variety of tumours. However, to what extent IKKε remodels cellular metabolism is currently unknown. Here, we used metabolic tracer analysis to show that IKKε orchestrates a complex metabolic reprogramming that affects mitochondrial metabolism and consequently serine biosynthesis independently of its canonical signalling role. We found that IKKε upregulates the serine biosynthesis pathway (SBP) indirectly, by limiting glucose-derived pyruvate utilisation in the TCA cycle, inhibiting oxidative phosphorylation. Inhibition of mitochondrial function induces activating transcription factor 4 (ATF4), which in turn drives upregulation of the expression of SBP genes. Importantly, pharmacological reversal of the IKKε-induced metabolic phenotype reduces proliferation of breast cancer cells. Finally, we show that in a highly proliferative set of ER negative, basal breast tumours, IKKε and PSAT1 are both overexpressed, corroborating the link between IKKε and the SBP in the clinical context.
Publication data is maintained in RPS. Visit https://rps.ucl.ac.uk
 More search options
UCL Researchers Show More
Author
Research Department of Oncology
Author
Dept of Computer Science
Author
Research Department of Oncology
Author
Cell & Developmental Biology
University College London - Gower Street - London - WC1E 6BT Tel:+44 (0)20 7679 2000

© UCL 1999–2011

Search by