Phosphoserine Aminotransferase 1: A Metabolic Enzyme Target of Cancers.

ABSTRACT

Phosphoserine aminotransferase 1 (PSAT1) catalyzes 3-phosphohydroxylpyruvate and glutamate into 3-phosphoserine and α-ketoglutamate. It integrates metabolic pathways critical for cell proliferation, survival, migration and epigenetics, such as glycolysis, de novo serine synthesis, citric acid cycle and one-carbon metabolism. The level of this enzyme has been disclosed to be closely related to the occurrence, progression and prognosis of cancers like non-small cell lung cancer, colorectal cancer, esophageal squamous cell carcinoma, breast cancer, etc. via metabolic catalyzation, PSAT1 offers anabolic and energic supports for these tumor cells, affecting their proliferation, survival, autophagy, migration and invasion. Such functions also influence the epigenetics of other noncancerous cells and drive them to serve tumor cells. Moreover, PSAT1 exerts a non-enzymatic regulation of the IGF1 pathway and nuclear PKM2 to promote EMT and cancer metastasis. Genetically manipulating PSAT1 alters tumor progression in vitro and in vivo. This paper reviews the role and action mechanism of PSAT1 in tumor biology and chemotherapy as well as the regulation of PSAT1 expression, exhibiting the perspective for PSAT1 as a new molecular marker and target for cancer diagnosis and treatment.