Fig. 1

A high level of intracellular GAA was associated with PDAC liver metastasis. A Hierarchical clustering analysis of 595 differential metabolites among normal (HPNE), primary cancer cells (PANC-1) and liver metastatic cancer cells (Capan-1). The color shade represents the relative expression level of metabolites. Principal component analysis (PCA) of original data consisting of 3281 Peaks (upper right). Venn analysis of differential metabolites between every two groups of pancreatic cancer cells (lower right). B Metabolic pathway analysis of differential metabolites between every two groups. The horizontal axis and the bubble size represented the impact factor of this pathway. The vertical axis and the bubble color represented the p value in the enrichment analysis. C GSEA showing arginine and proline metabolism enhanced in Capan-1 cells versus PANC-1 (GSE149103), and in liver metastases versus primary tumor (GSE42952). D Schematic of ornithine cycle and arginine metabolism. E Western blot showing expression of enzymes in arginine metabolism pathway. F Quantitative measurement of intracellular metabolites by LC–MS/MS. G Transwell migration assay of pancreatic cancer cells cultured in different conditions. GAA (1 mM). 100 × magnifying power. H Western blot showing RhoA expression in pancreatic cancer cells. I Schematic of mice models of orthotopic injection and splenic injection. J PCA analysis of the metabolites in PRMs and LMTs. K Metabolic pathway analysis of different metabolites between PRMs and LMTs. L Western blot showing GATM expression in PRM cells and LMT cells. M Quantitative measurement of intracellular GAA in PANC-1 PRM cells and LMT cells by LC–MS/MS. Data in (F-G) and (M) are presented as mean ± SEM by ordinary one-way ANOVA (Tukey’s multiple comparisons test) and unpaired student t test. * P < 0.05, ** P < 0.01, *** P < 0.001, **** P < 0.0001