Tumour glycolysis: the many faces of HIF.
We present a model for tumour metabolism that incorporates both microenvironmental (extracellular) and oncogenic (intracellular) influences. We explore the effects of the interaction between the hypoxic microenvironment and intracellular signalling on the glycolytic response of tumour tissue, finding that the glycolytic state is dependent on a delicately balanced interplay between the cellular hypoxic response, mediated by hypoxia-inducible factor-1alpha (HIF-1alpha), and growth-factor signalling cascades, which are frequently mutated in cancers. Our findings demonstrate the importance of considering both environmental and intracellular regulation when interpreting tumour metabolism for diagnostic or prognostic purposes. To illustrate this, we demonstrate the potential impact of this multi-factorial regulation on the kinetics of radiolabelled glucose analogues, used in positron emission tomography (PET).
Kelly
Catherine
C
Information Engineering, University of Oxford, Oxford OX13PJ, UK. ckelly@robots.ox.ac.uk
Smallbone
Kieran
K
Brady
Michael
M
D000818:Animals; D015687:Cell Hypoxia; D003198:Computer Simulation; D015972:Gene Expression Regulation, Neoplastic; D005947:Glucose / Q000378:metabolism*; D006019:Glycolysis; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism*; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008954:Models, Biological; D009154:Mutation; D009369:Neoplasms / Q000378:metabolism*; D049268:Positron-Emission Tomography; D015398:Signal Transduction / Q000502:physiology*
D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D036341:Intercellular Signaling Peptides and Proteins; D005947:Glucose