Xu 2014 Abstract IOC96

Xu R (2014) Exploring the role of IKKε in cancer metabolism. Mitochondr Physiol Network 19.11.

Link:

Xu R, Wilcz-Villega E, Bianchi K (2014)

Event: IOC96

Inflammation is a hallmark of cancer considered to be responsible for tumour survival and proliferation. Emerging evidence indicates that IкB kinase ε (IKKε) plays an important role both in inflammation and cancer. As a kinase, IKKε was previously reported to activate the transcription factor NF-кB downstream of Toll-like receptors [1], and also to be involved in the regulation of interferon (IFN) signalling by phosphorylating IRF-3 and IRF-7 [2]. Moreover, IKKε was recognised as an oncogene and is reported to be overexpressed in 30% of breast cancers and breast cancer cell lines [3]. More recently, IKKε has been also implicated in the regulation of energy balance in obese mice [4].

To investigate the role of IKKε in inflammation and understand more about its role as oncogene, we generated a 293-FLIP-IN cell line, in which expression of IKKε is induced by addition of doxycycline. In this cell line IKKε induction leads to phosphorylation of IRF-3 and production of IFN-β, confirming that the cell line is a perfectly suitable model to study IKKε. Our data show that the tumour promoting mechanism of IKKe is not limited to the activation of NFkB, but can also involve alterations in cellular metabolism. Preliminary data indicate that, when IKKe is constitutively active - being the driving oncogene – it diverts glucose from being fully oxidised in the mitochondria to other metabolic pathways, thus contributing to the Warburg effect, supporting cell proliferation.

Beside its role as an oncogene, IKKe could also contribute to malignant transformation upon activation of the innate immune response by rewiring cellular metabolism, highlighting a new aspect of how inflammation can contribute to tumorigenesis.

• O2k-Network Lab: UK London Bianchi K

Labels: MiParea: Patients  Pathology: Cancer 

Organism: Human  Tissue;cell: Other cell lines 

MITRAC12 

Affiliation

Barts Cancer Institute, Queen Mary, University of London

References

1. Shen RR, Hahn WC (2011) Emerging roles for the non-canonical IKKs in cancer. Oncogene 30:631-41. PubMed PMID: 21042276. Pubmed Central PMCID: PMC3235643. eng.
2. Trinchieri G (2010) Type I interferon: friend or foe? J Exp Med 207:2053-63. PubMed PMID: 20837696. Pubmed Central PMCID: PMC2947062. eng.
3. Boehm JS, Zhao JJ, Yao J, Kim SY, Firestein R, Dunn IF, et al (2007) Integrative genomic approaches identify IKBKE as a breast cancer oncogene. Cell 129:1065-79. PubMed PMID: 17574021. eng.
4. Chiang SH, Bazuine M, Lumeng CN, Geletka LM, Mowers J, White NM, et al (2009) The protein kinase IKKepsilon regulates energy balance in obese mice. Cell 138:961-75. PubMed PMID: 19737522. Pubmed Central PMCID: PMC2756060. eng.