Metabolism of pancreatic cancer: paving the way to better anticancer strategies

摘要

The landscape of metabolic pathways in pancreatic cancer cells. The metabolism of glucose, amino acids and lipids is largely reprogrammed, which is mainly due to changes in key enzymes and transporters. Furthermore, some of them are closely regulated by oncogenic KRAS. Additionally, micropinocytosis and autophagy are also promoted by mutant KRAS, but they are controlled by other regulatory mechanisms within pancreatic cancer cells as well. Long solid arrows imply shifts or bioconversions. The dotted arrow means positive regulation, whereas the blunt end means negative regulation. Red arrowheads following the enzymes, transporters, and processes represent the effects induced by mutant KRAS: upward means upregulation; downward means downregulation. The black symbols represent the changes induced by other or unknown reasons. In addition, those following tildes indicate that they are dually regulated under different conditions. ACLY, ATP citrate lyase; ASNS, asparagine synthetase; CARM1, coactivator-associated arginine methyltransferase 1; CS, citrate synthetase; F-6P, fructose 6-phosphate; F-1,6BP, fructose 1,6-bisphosphate; F-2,6BP, fructose 2,6-bisphosphate; GFPT1, glutamine:fructose 6-phosphate amidotransferase 1; G-6P, glucose 6-phosphate; HK1/2, hexokinase 1/2; HMGCR, 3-hydroxy-3-methylglutaryl coenzyme A reductase; HMG-CoA, 3-hydroxy-3-methylglutaryl coenzyme A; ME1, malic enzyme; MUFA, monounsaturated fatty acid; PFK1, phosphofructokinase 1; PRODH1, proline oxidase; PUFA, polyunsaturated fatty acid; RPE, ribulose-5-phosphate epimerase; SCD1, stearoyl-CoA desaturase; SFA, saturated fatty acid; TCA, tricarboxylic acid