Energy Metabolism Profiling of Human Colorectal Tumours

Abstract

Colorectal cancer (CRC) is a significant global health burden, and its early detection is crucial. Novel diagnostic and prognostic methods are required for improving patient treatment, survival and quality of life. One promising approach is the analysis and understanding of the metabolic reprogramming undergone by cancer cells. Here, by analysing the changes in transcript and protein contents, activities, pathway flux and energy metabolite ratios in post-operative CRC tumours, in comparison to adjacent healthy tissue, the energy metabolism was characterised at the molecular and functional levels. Greater expression of glucose transporter 1 and lactate dehydrogenase A (LDH), together with increased protein content and activity of LDH in tumours, suggested a higher glycolytic capability. Hexokinase transcripts, protein and activity were similar, whereas monocarboxylate transport transcripts and protein contents were lower in tumours. The creatine kinase transcripts and the adenylate kinase protein contents were lower in tumours, suggesting a functional decrease in the CRC energy transfer pathway. Notwithstanding this, oxidative phosphorylation was fully functional and exhibited higher catalytic efficiency (Vmax/Km_ADP) in tumours, whereas the cellular energy charge was slightly lower in tumours. Remarkably, higher OxPhos catalytic efficiency correlated with advancing CRC clinical stage. The data revealed that CRC tumours exhibit a hybrid energy metabolism phenotype where both glycolysis and oxidative phosphorylation are highly active.