Xu 2014 Abstract IOC96
| Xu R (2014) Exploring the role of IKKΞ΅ 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 IΠΊB kinase Ξ΅ (IKKΞ΅) plays an important role both in inflammation and cancer. As a kinase, IKKΞ΅ was previously reported to activate the transcription factor NF-ΠΊB 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, IKKΞ΅ was recognised as an oncogene and is reported to be overexpressed in 30% of breast cancers and breast cancer cell lines [3]. More recently, IKKΞ΅ has been also implicated in the regulation of energy balance in obese mice [4].
To investigate the role of IKKΞ΅ in inflammation and understand more about its role as oncogene, we generated a 293-FLIP-IN cell line, in which expression of IKKΞ΅ is induced by addition of doxycycline. In this cell line IKKΞ΅ induction leads to phosphorylation of IRF-3 and production of IFN-Ξ², confirming that the cell line is a perfectly suitable model to study IKKΞ΅. 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 β 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.
Labels: MiParea: Respiration, Patients
Stress:Mitochondrial Disease; Degenerative Disease and Defect"Mitochondrial Disease; Degenerative Disease and Defect" is not in the list (Cell death, Cryopreservation, Ischemia-reperfusion, Permeability transition, Oxidative stress;RONS, Temperature, Hypoxia, Mitochondrial disease) of allowed values for the "Stress" property. Organism: Human
Coupling state: OXPHOS
MITRAC12
Affiliation
Barts Cancer Institute, Queen Mary, University of London
