The role and mechanism of hypoxia-induced SLC6A8 up-regulation in HCC progression

Hypoxia is a hallmark of solid tumors and profoundly affects the malignant phenotypes of cancer cells. We find that the creatine transporter solute carrier family 6, member 8 (SLC6A8) is upregulated in hypoxic HCC cells. Hypoxia-induced creatine accumulation drives metabolic reprogramming and antagonizes parthanatos. Pharmacological inhibition of SLC6A8 represents a promising therapeutic strategy for HCC. Overall design: RNA-seq profiling of control (shNC) and SLC6A8-knockdown (shSLC6A8) HCC cells under hypoxia for 24 hours.