Fig. 1: PTEN loss or PI3K activation promotes glycolysis and PPP.
From: TRIM21 and PHLDA3 negatively regulate the crosstalk between the PI3K/AKT pathway and PPP metabolism
a Loss of the PTEN lipid phosphatase activity increases the GLUT1 levels (upper panel), glucose consumption and lactate production in the Pten null, CS, and GE mES cells compared with the isogenic WT cells. b Upper panel, a schematic illustrating [U-13C] glucose metabolism; lower panel, loss of the PTEN lipid phosphatase activity increases the levels of 13C-labeled glycolytic intermediates from G6P to PEP in the Pten null, CS, and GE mES cells compared with the isogenic WT cells. Glucose-6-phosphate (G6P), fructose-6-phosphate (F6P), fructose-1,6-bisphosphate (FBP), gyyceraldehyde-3-phosphate (G3P), phosphoenolpyruvate (PEP), pyruvate (Pyr), citrate (Cit), aconitate (Aco), α-ketoglutarate (α-KG), succinate (Suc), malate (Mal), oxaloacetate (Oxa). c Upper panel, a schematic illustrating [1,2-13C] glucose tracing into the oxidative arm of the PPP; lower panel, faster and higher levels of labeled 6-phosphogluconate (6PG) and ribose-5-phosphate (R5P) in the Pten null, CS, and GE mES cells compared with the WT cells. d Upper panel, a schematic illustrating [1,2-13C] glucose tracing into the nucleotide biosynthesis pathway; lower panel, increased levels of labeled nucleotides and NADPH production in the Pten null, CS, and GE mES cells compared with the WT cells. e,f Upper panels, increased PPP metabolites in the Pten null prostate cancer and T-ALL mouse models. Metabolites in the PPP were extracted from the anterior lobes of the Pb-Cre−;PtenL/L and Pb-Cre+;PtenL/L mice (e) or the thymus of the VEC−Cre−;PtenL/L and VEC−Cre+;PtenL/L mice (f) by box plots. Median and quartile values are provided by the central line and box boundaries. Whiskers show min to max values. Sedoheptulose-7-phosphate (S7P), phosphoribosyl pyrophosphate (PRPP). n = 7 (e), n = 3 (f), numbers of independent mouse samples. a–d, cell extracts from Pten mutant cell lines were prepared and analyzed using LC-MS. Data are presented as fold changes and the mean ± SD and were compared with the WT cells. Each experiment was performed n = 4 (a) and n = 3 (b–d) independent times. *p < 0.05, **p < 0.001, ***p < 0.001, based on Student’s t test (two-sided ANOVA). See also Supplementary Fig. 1. Source data are provided as a Source Data file.
