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. 2023 Aug 18;4(9):101162. doi: 10.1016/j.xcrm.2023.101162

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© 2023 The Author(s)

This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

PMC Copyright notice

The GLUT1/ALDOB/G6PD axis drives glucose metabolic reprogramming in glucomet-PDAC

(A) Relative G6PD enzyme activity in representative organoids of glucomet-PDAC (n = 6) and lipomet-PDAC (n = 6).

(B) Relative G6PD enzyme activity in vector- and ALDOB-overexpressing organoids (n = 3).

(C) Relative abundance of oxidative PPP metabolites in control and ALDOB-overexpressing organoids (n = 3).

(D and E) Relative abundance of oxidative PPP metabolites in control, GLUT1 knockdown, ALDOB overexpression, GLUT1 knockdown, and ALDOB overexpression organoids (n = 3).

(F) Endogenous ALDOB and G6PD interactions in PDAC organoids detected by immunoprecipitation (IP) experiments.

(G–I) TCGA patients with PDAC (n = 156) were divided into GLUT1^high/ALDOB^low, GLUT1^low/ALDOB^high, and others based on GLUT1 and ALDOB expression levels. Samples with expression of GLUT1 in the top 40% and expression of ALDOB in the last 40% were named GLUT1^high/ALDOB^low, while samples with expression of ALDOB in the top 40% and expression of GLUT1 in the last 40% were named GLUT1^low/ALDOB^high. GSEA enrichment plot for GLUT1^high/ALDOB^low group versus GLUT1^low/ALDOB^high group of fatty acid metabolism (G), pentose phosphate pathway (H), and glycolysis/gluconeogenesis (I) signature genes.

(J) Representative images of immunohistochemical staining show high or low GLUT1 staining and high or low ALDOB staining in PDAC TMA (n = 285). Scale bar, 50 μm. Patients were divided into four groups based on ALDOB and GLUT1 expression levels: ALDOB^high (++), ALDOB expression >50%; ALDOB^low (+), ALDOB expression <50%; GLUT1^high (++), GLUT1 expression >50%; and GLUT1^low (+), GLUT1 expression <50%.

(K) Kaplan-Meier survival curves based on the expression of GLUT1 and ALDOB in 285 patients with PDAC.

(L) Summary scheme highlighting the roles of the GLUT1/ALDOB/G6PD axis in glucose reprogramming.

Data are presented as the mean values ± SEMs, and statistical significance was computed by unpaired Student’s t test (A–E). Statistical significance was computed by log-rank test (K).