Development of novel trans-omics method and the significance of polyamine metabolism in Cancer Stem Cells

Abstract

The development of novel analytical methods based on bioinformatics and computational modelling is expected to offer innovative approaches in human medical science. Recently, we have performed computational analyses using some transcriptome and metabolome datasets for one of the human esophagus cancer cell line, TE-4, resulting in the generation of a model to explain the change of flow of biological reaction pathways. We extended this method in the current study to examine for differences in the behaviour between Cancer Stem Cells (CSCs) and non-CSCs. Our new approach revealed a previously uncharacterized role for the ornithine metabolic pathway in conferring chemo-resistance in CSC. In our analysis, we showed that CSCs reduce polyamine levels to resist chemotherapy. In contrast, polyamines in non-CSCs are maintained at a high level. The high polyamine level may act to inhibit lysine-specific demethylase 1A (LSD1) activity and induce epigenetic changes that increase cell survival, as suggested in previous reports.