Fig. 6. The expression levels of ATF4, GLUT5, and ALDOB positively correlate with each other in GBM specimens and indicate a poor prognosis in GBM patients.
a, b Sixty-eight human primary GBM specimens were immunohistochemically stained with indicated antibodies. Representative photos of tumors are shown (a). Immunohistochemistry staining scores of ATF4, GLUT5, and ALDOB were analyzed by Spearman’s correlation (b). Note that size (ranging from 1 to 7) of the dots represents the number of specimen(s) appearing on the graphs. Scale bar, 50 µm (a). c The survival time for 68 patients with low (1–4 staining scores, blue curve) versus high (5–8 staining scores, red curve) levels of ATF4, GLUT5, and ALDOB were compared. Empty circles represent censored data from patients alive at last clinical follow-up. P values were determined by the two-tailed log-rank test. d A mechanism of ATF4-dependent fructolysis supports GBM growth under glucose-deprived condition. A model shows that ATF4, which is activated upon glucose deprivation, induces expression of GLUT5 and ALDOB. High levels of GLUT5 and ALDOB drive fructolysis to maintain GBM growth under glucose-deprived condition. F1P fructose 1-phosphate, GA glyceraldehyde, DHAP dihydroxyacetone phosphate, GAP glyceraldehyde 3-phosphate. Source data are provided as a Source Data file.