Stabilization of Notch1 and β-catenin in response to ER- breast cancer-specific up-regulation of PSAT1 mediates distant metastasis

•PSAT1 is upregulated in metastatic breast cancer.•PSAT1 promotes distant metastasis in vivo.•PSAT1-facilitated aggressiveness of breast cancer cells promotes early metastasis.•PSAT1 activates Wnt/β-catenin and notch signaling pathways by stabilizing the respective proteins.•Activation of β-catenin and notch signaling mediates PSAT1-induced aggressiveness of breast cancer cells.•Aberrant upregulated PSAT1 is a potential biomarker of early metastasis in breast cancer. Breast cancer has the highest incidence in women worldwide, with a mortality rate second only to lung cancer. Distant metastasis is the major cause of breast cancer-induced death. While upregulation of phosphoserine aminotransferase 1 (PSAT1) has been reported in several cancer types, its specific roles in breast cancer and potential involvement in distant metastasis remain unclear. In our study, PSAT1 was upregulated in metastatic breast cancer and promoted distant metastasis both in vitro and in vivo. Data obtained from transwell and wound healing, colony, sphere assays and detection of various malignant phenotypic markers showed that PSAT1 mediates distant metastasis by promoting invasion, migration, proliferation, anti-apoptosis, stemness and angiogenesis in breast cancer cells. Mechanistically, PSAT1 activated Notch and β-catenin signaling pathways, leading to enhanced distant metastasis. The clinical relevance of PSAT1 in breast cancer was additionally investigated, which revealed associations of poorer patient prognosis with high PSAT1 mRNA and protein expression. In summary, PSAT1 is a critical molecular regulator of distant metastasis that may effectively serve as a marker of poor prognosis in breast cancer.