Fig. 5: Lactylation of NUDT21 enhances resistance to cuproptosis by targeting FDX1.

a, b The cell viability of KYESE30 cells treated with l-lactate, d-lactate (a), oxamate, β-alanine, or stiripentol (b) in response to elesclomol-Cu²⁺ or disulfiram-Cu²⁺, as measured by CCK8. c The cell viability of NUDT21-knockdown KYSE30 cells following treatment with elesclomol-Cu²⁺, with or without l-lactate (20 mM), as measured by CCK8. d The cell viability of NUDT21 WT- or K23R-overexpressing KYSE30 cells was measured by CCK8 after treatment with elesclomol-Cu²⁺, with or without l-lactate (20 mM). e The cell viability of KYESE30 cells transfected with the indicated plasmids or siRNAs in response to elesclomol-Cu²⁺, as measured by CCK8. f, g TTM (1 μM) treatment (f) or FDX1 depletion (g) reversed the growth inhibition induced by NUDT21 knockdown in KYSE30 cells treated with elesclomol-Cu²⁺. h, i Subcutaneous tumors of nude mice with control or NUDT21-knockdown KYSE30 cells (n = 6). Mice were treated with or without elesclomol. Tumor volume (h) and weight (i) were measured. j, k Subcutaneous tumors of nude mice with NUDT21 WT- or K23R-overexpressing KYSE30 cells (n = 6). Mice were treated with or without elesclomol. Tumor volume (j) and weight (k) were measured. Data are presented as mean ± SD; P value was calculated by two-way ANOVA (a–h, j) and Student’s t-test (i, k).