Yang Xue, Li Chaojie, Chen Yuping
Institute of Pharmacy & Pharmacology, School of Pharmaceutical Science, University of South China, Hengyang 410001, China.
Curr Cancer Drug Targets. 2023;23(3):171-186. doi: 10.2174/1568009622666220829105300.
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.
磷酸丝氨酸转氨酶1(PSAT1)催化3-磷酸羟基丙酮酸和谷氨酸生成3-磷酸丝氨酸和α-酮戊二酸。它整合了对细胞增殖、存活、迁移和表观遗传学至关重要的代谢途径,如糖酵解、从头丝氨酸合成、柠檬酸循环和一碳代谢。已发现该酶的水平与非小细胞肺癌、结直肠癌、食管鳞状细胞癌、乳腺癌等癌症的发生、发展和预后密切相关。通过代谢催化,PSAT1为这些肿瘤细胞提供合成代谢和能量支持,影响它们的增殖、存活、自噬、迁移和侵袭。这些功能还影响其他非癌细胞的表观遗传学,并促使它们为肿瘤细胞服务。此外,PSAT1对IGF1途径和核PKM2发挥非酶调节作用,以促进上皮-间质转化和癌症转移。对PSAT1进行基因操作会改变肿瘤在体外和体内的进展。本文综述了PSAT1在肿瘤生物学和化疗中的作用及作用机制以及PSAT1表达的调控,展示了将PSAT1作为癌症诊断和治疗的新分子标志物和靶点的前景。