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. 2023 Mar 2;83(9):1426–1442. doi: 10.1158/0008-5472.CAN-22-3000

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©2023 The Authors; Published by the American Association for Cancer Research

This open access article is distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) license.

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Figure 5. De novo cysteine synthesis does not contribute to the cysteine pool of lung tumors. A, Schematic for the generation of KrasG12D; p53−/− and KrasG12D; p53−/−; Nrf2D29H LUAD, and Rb1−/−; p53−/−; MycT58A/+ or Rb1−/−; p53−/−; MycT58A/T58A SCLC GEMM tumors. B, Analysis of the fraction labeling in serine, glycine, cystathionine, glutathione, cysteine, and γ-glutamylcysteine in normal lung tissues (N = 8) compared with Nrf2WT LUAD and (N = 10), Nrf2D29H LUAD tumors (N = 10) and their matched serum from normal (N = 8), Nrf2WT (N = 5), and Nrf2D29H (N = 5) following infusion with 1-[13C1]-serine. C, Analysis of the fraction labeling in serine, glycine, cystathionine, glutathione, cysteine, and γ-glutamylcysteine in normal lung tissues (N = 8) compared with SCLC tumors (N = 9), and their matched serum normal (N = 8) and SCLC (N = 9) following infusion with 1-[13C1]-serine. 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 CBS and CSE for each tissue. HSP90 was used for the loading control. *, P < 0.05; ****, P < 0.0001. Cth, cystathionine; Cys, cysteine; Gly, glycine; GSH, glutathione; γ-Glu-Cys, γ-glutamylcysteine; Ser, serine. (A, Created with BioRender.com.) — 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. B, Analysis of the fraction labeling in serine, glycine, cystathionine, glutathione, cysteine, and γ-glutamylcysteine in normal lung tissues (N = 8) compared with Nrf2^WT 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-[¹³C₁]-serine. C, Analysis of the fraction labeling in serine, glycine, cystathionine, glutathione, cysteine, and γ-glutamylcysteine in normal lung tissues (N = 8) compared with SCLC tumors (N = 9), and their matched serum normal (N = 8) and SCLC (N = 9) following infusion with 1-[¹³C₁]-serine. 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 CBS and CSE for each tissue. HSP90 was used for the loading control. *, P < 0.05; ****, P < 0.0001. Cth, cystathionine; Cys, cysteine; Gly, glycine; GSH, glutathione; γ-Glu-Cys, γ-glutamylcysteine; Ser, serine. (A, Created with BioRender.com.)