Fig. 6.
Aspartate metabolism in solid tumor. The high expression of SLC1A3 in tumor cells promoted the absorption of aspartate, supplemented the low aspartate state caused by ASNase, and produced resistance to ASNase therapy. SLC25A22 expressed on mitochondria can increase the intake of mitochondrial aspartate, promote mitochondrial function and reduce oxidative stress. KRAS activates NRF2-ATF4 axis through PI3K/AKT signaling pathway, promotes ASNS transcription and increases intracellular asparagine concentration. Asparagine (Asn) can bind to SRC family tyrosine kinase LCK to assist in phosphorylation of LCK at Tyr394. Enhance LCK activity and T cell receptor signaling, and promote AKT, RAS activation. Asparagine can inhibit AMPK signaling pathway activity by binding to LKB1. In T lymphocytic leukemia cells, ATF4 binds to ASNS gene promoter through ZBTB1 (Zinc Finger and BTB domain-containing protein 1), promotes ASNS transcription, increases intracellular Asparagine concentration. Created with BioRender.com. (The red blunt line represents inhibition)