Figure 5.

De novo cysteine synthesis does not contribute to the cysteine pool of lung tumors. A, Schematic for the generation of Kras^G12D; p53^−/− and Kras^G12D; p53^−/−; Nrf2^D29H LUAD, and Rb1^−/−; p53^−/−; Myc^T58A/+ or Rb1^−/−; p53^−/−; Myc^T58A/T58A SCLC GEMM tumors. Created with Biorender.com. B, Analysis of the fraction labeling in serine, glycine, cystathionine, glutathione, cysteine and γ-glutamylcysteine in normal lung tissues (N=8) compared to Nrf2^WT lung adenocarcinoma (LUAD) and (N=10), Nrf2^D29H LUAD tumors (N=10) and their matched serum from normal (N=8), Nrf2^WT (N=5), and Nrf2^D29H (N=5) following infusion with 1-[¹³C₃]-serine. C, Analysis of the fraction labeling in serine, glycine, cystathionine, glutathione, cysteine and γ-glutamylcysteine in normal lung tissues (N=8) compared to small cell lung cancer (SCLC) tumors (N=9), and their matched serum normal (N=8) and SCLC (N=9) following infusion with 1-[¹³C₃]-serine. N.B. the control lung samples in C are the same as in B. D, Fractional contribution of serine to intracellular cysteine synthesis in LUAD and SCLC. Cysteine labeling was normalized to the fraction labeling of serine in each tissue. For B-D, data are presented as mean ± SD. N.D., not detected. E, Immunoblots of cystathionine β-synthase (CBS) and cystathionine γ-lyase (CSE) for each tissue. HSP90 was used for the loading control. *p < 0.05, **p < 0.01, ***p < 0.001, and ****p < 0.0001. Ser, serine; Cth, cystathionine; Cys, cysteine; Gly, glycine; GSH, glutathione; γ-Glu-Cys, γ-glutamylcysteine