Fig. 10

Illustration on the circulation of essential substances in and out of cancer cell. Glucose enters cancer cell through Glut1, undergoing glycolysis, forming pyruvate. Pyruvate does not go into mitochondria to synthesize Acetyl CoA, instead, it is directly exported out of cell or becomes lactate and excreted out of cell by membrane transporter MCT. Extracellular glutamines serve as fuels for the citric acid cycle. The intermediates succinate and fumarate are transported out of cell through transporters SLC13A3 and SLC26 respectively, causing the upregulation of these two metabolites in PDX serum. Amino acids get into cell through transporters SLC7A5 and SLC1A5. Tryptophan specifically, flow into cell through SLC1A5, degrade into kynurenine with the help of enzymes TDO and IDO. Kynurenine is then transported out of cell through SLC7A5. Solid black arrow denotes up or down regulation of differential metabolites found in PDX1 vs control, whereas solid gray arrow denotes the differential metabolites found in PDX2 vs control. *: P-value < 0.05; **: P-value < 0.01; ***: P-value < 0.001. Abbreviations: MCT, Monocarboxylate Transporter; Glut1, Glucose Transporter 1; SLC1A5, Solute Carrier Family 1 Member 5; SLC7A5, Solute Carrier Family 7 Member 5; SLC26, solute carrier 26; SLC13A3, Solute carrier Family 7 Member 5; TCA Cycle, Citric Acid Cycle; AAs, Amino Acids; Trp, Tryptophan; Kyn, Kynurenine