Correlation between amino acid metabolism and self-renewal of cancer stem cells: Perspectives in cancer therapy

Table 1 Summary of the role and mechanism of amino acid metabolism in cancer stem cells

Amino acid metabolism	Possible mechanisms in CSCs	Role in CSC properties
Methionine metabolism	Direct nutrients; Genetic modification; DNA biosynthesis	Self-renewal; tumorigenicity
Tryptophan metabolism	Immune escape and resistance; regulates stem genes and signal pathway	Self-renewal; survival
Threonine metabolism	Upregulated in colon CSCs (HCT116), but mechanism is unknown	Self-renewal
Lysine metabolism	Reduces ROS and activates Wnt pathway	Self-renewal
Leucine metabolism	Regulates CD13+ CSCs survival in hepatocellular carcinoma, but mechanism is unknown; Inhibits stemness and growth of EpCAM+ hepatocellular carcinoma stem cells by activating MTORC1	Stemness; survival
Valine metabolism	Regulates CD13+ CSCs survival in hepatocellular carcinoma, but mechanism is unknown	survival
Phenylalanine metabolism	Unknown	Unknown
Isoleucine metabolism	Inhibits stemness and growth of EpCAM+ hepatocellular carcinoma stem cells by activating MTORC1	Stemness
Histidine metabolism	Unknown	Unknown
Glycine metabolism	Direct nutrients within a certain range; epigenetic modification; DNA synthesis; regulates redox homeostasis; carries out TCA cycle	Self-renewal; survival; tumorigenicity; metastasis
Serine metabolism	Regulates redox homeostasis; shunts glucose metabolism; carries out TCA cycle; influences T cell proliferation	Self-renewal; survival; tumorigenicity; stemness; metastasis; resistance
Glutamine metabolism	Direct nutrients; carries out TCA cycle; synthesis of nucleic acids; maintains redox balance; regulates tumor immunity	Self-renewal; survival; tumorigenicity; stemness; resistance
Glutamate metabolism	Carries out TCA cycle; participates serine metabolism; maintains redox balance	Self-renewal; survival; tumorigenicity; stemness
Cysteine metabolism	Mainly maintains redox balance	Self-renewal; survival; tumorigenicity; resistance; metastasis
Aspartate metabolism	Replenishes TCA cycle; synthesis of nucleic acids	Survival
Asparagine metabolism	Replenishes TCA cycle; synthesis of nucleic acids; exchanges amino acids	Survival
Alanine metabolism	Upregulated in breast CSCs, but mechanism is unknown; regulates T cell function	Self-renewal;stemness; tumorigenicity
Arginine metabolism	Participates in cell proliferation and urea cycle; regulates tumor immunity	Self-renewal
Proline metabolism	Maybe epigenetic modification and transform steadily; synthesize collagen	Self-renewal; stemness; metastasis
Tyrosine metabolism	Provides energy; Foxd3 acetylation	Self-renewal

CSC: Cancer stem cell; TCA cycle: Tricarboxylic acid cycle.