Description

Trans-omics Analysis Revealed Novel Functions of the Cancer Specific Metabolic Pathway in Cancer Stem Cells

Masamitsu Konno^1,2, Ayumu Asai^1,2, Hidetoshi Matsui⁴, Jun Koseki², Taroh Satoh¹, Yuichiro Doki³, Masaki Mori³, Hideshi Ishii^1,2

¹Department of Cancer Frontier Science; ²Department of Medical Data Science; ³Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Suita, Osaka, Japan; ⁴Shiga University Graduate School of Medicine, Shiga, Japan

Bioinformatics studies, computational modelling and theoretical analyses are expected to offer innovative approaches in human medical science. By utilizing the single-cell revel analysis, we performed computational analyses and made predictions using transcriptome and metabolome datasets obtained from fluorescence-based visualisations with a degron motif originating in ornithine decarboxylase of chemotherapy-resistant cancer stem cells in the human esophagus. This approach revealed an uncharacterized role for the ornithine metabolic pathway in the survival of chemotherapy-resistant cancer stem cells. In our analysis, cancer stem cells showed decreased polyamine levels during chemotherapy and resisted this therapy. These results suggest that polyamines inhibit LSD1 enzyme activity and change gene expression levels to influence cell survival. In this study, we showed that cancer stem cells reduce polyamine levels to resist chemotherapy. In contrast, polyamines in non- cancer stem cells are maintained at a high level. This high polyamine level may act to inhibit LSD1 activity and induce epigenetic changes that increase cell survival, as suggested in previous reports.