Objective  Reprogrammed metabolism is a hallmark of cancer, and an array of key enzymes are deregulated in various cancer settings. Phosphoserine aminotransferase 1 (PSAT1), which converts 3-phosphohydroxypyruvate to phosphoserine, enhances malignant traits in a few solid cancers including lung adenocarcinoma, glioblastoma, breast cancer, and colorectal cancer. In this study, we investigated the function of PSAT1 in gastric cancer (GC).

  Methods  The Kaplan-Meier plotter database was used to analyze the association between PSAT1 expression and overall survival (OS) rate in patients with GC. PSAT1 mRNA levels were determined using RT-qPCR in a panel of GC cell lines and the immortalized human gastric epithelial cell line GES1. Lentiviral particles expressing PSAT1 were packaged, and then BGC823 and NCI-N87 cells were transduced. The cell counting Kit-8 (CCK-8) and clone formation assay were used to test the role of PSAT1 in the proliferation of GC cells in vitro. Additionally, a xenograft model was established in immunodeficient mice to detect the growth of GC cells in vivo.

  Results  Higher PSAT1 expression indicated longer OS in patients with GC (P=1.7e-6, HR=0.52). PSAT1 mRNA expression in GC KATOIII, AGS, SNU16, NCI-N87, MKN45, BGC823, MGC803, and SGC7901 cell lines was markedly lower than that of GES1 cells. CCK8 assay showed that enforced expression of PSAT1 significantly attenuated proliferation in BGC823 （120 hr, P<0.000 1 and NCI-N87（96 hr, P<0.000 1）cells in vitro . Clone formation assay also demonstrated that PSAT1 overexpression reduced the clone numbers of BGC823 (P=0.029 6) and NCI-N87 (P=0.036 5) cells. Additionally, PSAT1 significantly suppressed growth of the subcutaneously injected NCI-N87 cells in Balb/c nude mice, as evidenced by the reduced tumor weights in PSAT1 group relative to control group (n=7, P=0.009 1)

  Conclusions  The higher expression of PSAT1 indicated favorable prognosis in patients with GC. Moreover, the PSAT1 expression decreased in most GC cell lines compared with that in GES1, and the high expression of PSAT1 markedly inhibited the proliferation of GC cells in vitro and in vivo.