Fig. 8.
Arginine metabolism in tumor cells. Arginine depletion can increase the phosphorylation level of GCN2 in hepatocellular cancer cells, activate GCN, increase the expression level of SLC7A11 and increase the uptake of arginine. Activated GCN2 can also be mediated by p21 cell cycle arrest; GCN2 also increases protein synthesis by activating mTORC1 via sestrin. ARG2 in the mitochondria of melanoma cells increases transfer-promoting gene transcription via the p66SC-H2O2-Stat3 axis. Myeloid cells can promote intracellular p38 and ARG1 transcription by receiving tumor cell-derived CSF and activation of STAT3. In addition, low pH of tumor microenvironment also promoted ARG1 transcription through H+ activation of intracellular cAMP-CREB axis. IL-6 and IL-8 promote ARG1 transcription by activating the PI3K/AKT pathway. The arginine metabolism of myeloid cells with high expression of ARG1 was enhanced, and the arginine metabolism of T cells was inhibited, and the tumor immunity was inhibited. Created with BioRender.com. (The red blunt line represents inhibition)