joint analysis of metabolome and transcriptome in system Xc- regulating glucose deprivation-induced cell death

Glucose depletion is common in the solid tumor microenvironment due to deficiency of blood supply. However, rapid growing carcinoma always rely heavily on the glucose metabolism to meet the energy needs of vital activity, making tumor cells sensitive to glucose deprivation. Therefore, inhibition of glucose transporter (GLUTs) is one strategy to kill cancer cells. Interestingly, it was recently discovered that glucose deprivation-induced necrosis probably relies on the system Xc-, the antiporter of cystine and glutamate which has been well studied in the ferroptosis. On the other side, inhibitors of system Xc- are apt to save cells under glucose depletion condition instead of promoting cell death, though both inhibition of system Xc- and glucose starvation drastically induce ROS generation. Here in our present study, we tried to figure out the interaction of glucose starvation and system Xc- inhibition in head and neck squamous cell carcinoma, providing useful suggestions for clinical treatment of malignant tumors.