Metabolic profiling reveals potential metabolic markers associated with Hypoxia Inducible Factor-mediated signalling in hypoxic cancer cells

Armitage, E. G. , Kotze, H. L., Allwood, J. W., Dunn, W. B., Goodacre, R. and Williams, K. J. (2015) Metabolic profiling reveals potential metabolic markers associated with Hypoxia Inducible Factor-mediated signalling in hypoxic cancer cells. Scientific Reports, 5, 15649. (doi: 10.1038/srep15649) (PMID:26508589) (PMCID:PMC4623531)

Abstract

Hypoxia inducible factors (HIFs) plays an important role in oxygen compromised environments and therefore in tumour survival. In this research, metabolomics has been applied to study HIFs metabolic function in two cell models: mouse hepatocellular carcinoma and human colon carcinoma, whereby the metabolism has been profiled for a range of oxygen potentials. Wild type cells have been compared to cells deficient in HIF signalling to reveal its effect on cellular metabolism under normal oxygen conditions as well as low oxygen, hypoxic and anoxic environments. Characteristic responses to hypoxia that were conserved across both cell models involved the anti-correlation between 2-hydroxyglutarate, 2-oxoglutarate, fructose, hexadecanoic acid, hypotaurine, pyruvate and octadecenoic acid with 4-hydroxyproline, aspartate, cysteine, glutamine, lysine, malate and pyroglutamate. Further to this, network-based correlation analysis revealed HIF specific pathway responses to each oxygen condition that were also conserved between cell models. From this, 4-hydroxyproline was revealed as a regulating hub in low oxygen survival of WT cells while fructose appeared to be in HIF deficient cells. Pathways surrounding these hubs were built from the direct connections of correlated metabolites that look beyond traditional pathways in order to understand the mechanism of HIF response to low oxygen environments.

• Item Type: Articles
• Additional Information: Funded by the Biotechnology and Biological Sciences Research Council (BBSRC) and the Engineering and Physical Research Council (EPSRC) grants BB/C008219/1 and BB/G530225/1.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Armitage, Dr Emily Grace
• Authors: Armitage, E. G., Kotze, H. L., Allwood, J. W., Dunn, W. B., Goodacre, R., and Williams, K. J.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Journal Name: Scientific Reports
• Publisher: Nature Publishing Group
• ISSN: 2045-2322
• ISSN (Online): 2045-2322
• Copyright Holders: Copyright © 2015 Armitage, E.G. et al.
• First Published: First published in Scientific Reports 5:15649
• Publisher Policy: Reproduced under a creative commons license