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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 4. Tumorigenesis of liver and pancreas induces downregulation of de novo cysteine synthesis. A, Schematic for the generation of Myc; p53−/− HCC and KrasG12D; p53+/− PDAC GEMM tumors. B, Analysis of the fraction labeling in serine, glycine, cystathionine, glutathione, cysteine, and γ-glutamylcysteine in liver tissues (N = 8) compared with HCC tumors (N = 8) and their matched serum normal (N = 8) and HCC (N = 5) following infusion with 1-[13C1]-serine. C, Analysis of the fraction labeling in serine, glycine, cystathionine, glutathione, cysteine, and γ-glutamylcysteine in pancreas tissues (N = 5) compared with PDAC tumors (N = 5) and their matched serum from normal (N = 5) and PDAC (N = 5) following infusion with 1-[13C1]-serine. D, Fractional contribution of serine to intracellular cysteine synthesis in HCC and PDAC. Cysteine labeling was normalized to the fraction labeling of serine in each tissue. One healthy pancreas sample was excluded because of a division error. 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 < 0.01. Cth, cystathionine; Cys, cysteine; Gly, glycine; GSH, glutathione; γ-Glu-Cys, γ-glutamylcysteine; Ser, serine. (A, Created with BioRender.com.) — Tumorigenesis of liver and pancreas induces downregulation of de novo cysteine synthesis. A, Schematic for the generation of Myc; p53^−/− HCC and Kras^G12D; p53^+/− PDAC GEMM tumors. B, Analysis of the fraction labeling in serine, glycine, cystathionine, glutathione, cysteine, and γ-glutamylcysteine in liver tissues (N = 8) compared with HCC tumors (N = 8) and their matched serum normal (N = 8) and HCC (N = 5) following infusion with 1-[¹³C₁]-serine. C, Analysis of the fraction labeling in serine, glycine, cystathionine, glutathione, cysteine, and γ-glutamylcysteine in pancreas tissues (N = 5) compared with PDAC tumors (N = 5) and their matched serum from normal (N = 5) and PDAC (N = 5) following infusion with 1-[¹³C₁]-serine. D, Fractional contribution of serine to intracellular cysteine synthesis in HCC and PDAC. Cysteine labeling was normalized to the fraction labeling of serine in each tissue. One healthy pancreas sample was excluded because of a division error. 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 < 0.01. Cth, cystathionine; Cys, cysteine; Gly, glycine; GSH, glutathione; γ-Glu-Cys, γ-glutamylcysteine; Ser, serine. (A, Created with BioRender.com.)