Psat1-flox Mouse

Psat1, also known as phosphoserine aminotransferase 1, is an enzyme in the serine biosynthesis pathway (SBP) [1-10]. The SBP is a branch of glycolysis, and Psat1 is one of its three key enzymes. It plays a crucial role in metabolism by producing metabolites like α-ketoglutarate (α-KG) and glutamine, which are involved in bioenergetics, biomass generation, and serving as cofactors for chromatin modifiers [1,7].

Gene inactivation studies in mice revealed that Psat1 controls muscle stem cell (MuSC) activation and expansion of myogenic progenitors [1]. Psat1 ablation led to defective MuSC expansion and impaired muscle regeneration [1].

Additionally, in tumors, targeting Psat1 has shown potential therapeutic effects. For example, in tumors with the p53-72Pro variant, depletion of PSAT1 restored the interaction between p5372P and PGC-1α, suppressing metastasis [2]. In triple-negative breast cancer, the miR-195-5p/PSAT1 feedback loop was identified, suggesting a potential targeted therapy [3]. In estrogen receptor-negative breast cancer, PSAT1 promoted metastasis via the p-AKT/SP1/ITGA2 axis [4]. In colorectal cancer, PSAT1 knockdown enhanced cell migration, invasion, proliferation, and the EMT process by regulating the PI3K/AKT signaling pathway [5]. In clear cell renal cell carcinoma, PSAT1 was associated with patient prognosis and was used to develop a new nomogram model for prognosis estimation [6].

In conclusion, Psat1 is essential for muscle stem cell activation and muscle regeneration [1]. In the context of diseases, especially cancer, studies on Psat1 gene knockout or knockdown models have provided insights into its role in tumor metastasis and prognosis, suggesting it could be a potential therapeutic target [2-6].