Fig. 6: The lactate-NUDT21-FDX1-cuproptosis axis represents a promising therapeutic target for ESCC.
From: NUDT21 lactylation reprograms alternative polyadenylation to promote cuproptosis resistance

a, b Subcutaneous tumors were subjected to FDX1 staining. Scale bars, 100 μm. Quantitative results of FDX1 staining were presented (n = 6). c Quantitative results of FDX1 staining in ESCC samples stratified by NUDT21 and LDHA levels (n = 60, 65, 67, and 59, respectively). d High levels of NUDT21 and LDHA are correlated with the lowest overall survival rate in the ESCC cohort. e Representative IHC images of K23-lactylated NUDT21, LDHA, and FDX1 staining in serial ESCC sections. Scale bars, 100 μm. f Scatter plots illustrating a positive correlation between LDHA and K23-lactylated NUDT21 levels (left) and a negative correlation between FDX1 and K23-lactylated NUDT21 levels (right) in the ESCC cohort (n = 251). g Elevated levels of K23-lactylated NUDT21 are associated with reduced overall survival rate in the ESCC cohort (n = 251). h, i Subcutaneous tumors of nude mice with KYSE30 cells (n = 6). Mice were treated with saline, elesclomol, stiripentol, or elesclomol + stiripentol. Tumor volume (h) and weight (i) were measured. j Schematic model illustrating the role of the lactate-NUDT21-FDX1-cuproprosis axis in ESCC. Data are presented as mean ± SD; P value was calculated by Student’s t-test (a–c, i), log-rank test (d, g), Pearson correlation analysis (f), and two-way ANOVA (h).