Fig. 7: Inverse correlation of SPOP and ASCT2 levels in breast cancer tissues and their association with patient survival.

a, b Representative images of SPOP and ASCT2 staining in consecutive breast tissues (normal VS. tumor). Green box (a) and arrow (b) indicate normal region, and red box (a) and arrow (b) indicates tumor region. c, d The relative proportion of SPOP (c) and ASCT2 (d) IHC staining in adjacent non-tumor and tumor tissues of breast. e The correlation analysis between SPOP and ASCT2 in breast tumor sections. f The association of SPOP and ASCT2 expression with overall survival in breast cancer patients. Survival fractions were plotted using the Kaplan–Meier method (Log-rank test). g, h Paired human breast normal and tumor tissues were analyzed by targeted metabolomics, and relative abundance of glutamine (g), glutamine/glutamate ratio (h) were compared between each individual pair of normal vs. tumor tissues. n = 12; Two-tailed, paired t test. i A working model (created in Adobe Illustrator). Under glutamine-rich condition, SPOP forms dimer to promote ASCT2 ubiquitylation and degradation. Under glutamine-deprivation, GRK2 phosphorylates SPOP to inhibit its dimerization, which triggers SPOP self-ubiquitylation and degradation, leading to increased glutamine metabolism. Source data are provided as a Source Data file.