Background: Accumulating evidence indicates that PSAT1 not only reprogrammed metabolic function but also exhibits “moonlighting” functions in promoting tumor malignancy. However, the underlying molecular mechanisms of PSAT1 promoting ER-negative breast cancer cell migration need further investigation. Methods: Briefly, the PSAT1 and ITGA2 expression in cells and tissues was detected using qRT-PCR, immunofluorescence staining and western blot assay. The effect of PSAT1 and ITGA2 was verified both in vitro and in vivo. RNA-seq analysis explored a series of differently expressed genes. The regulation between SP1 and ITGA2 was investigated by ChIP analysis. Results: We reported PSAT1 was highly expressed in ER-breast cancer tissues and tumor cells and positively correlated with metastasis. Moreover, RNA-seq analysis explored a series of differently expressed genes, including ITGA2, in PSAT1 overexpressed cells. Mechanistically, PSAT1 facilitated breast cancer metastasis via the p-AKT/SP1/ITGA2 axis. We further elucidated that PSAT1 promoted the entry of SP1 into the nucleus through the upregulation of p-AKT and confirmed ITGA2 is a target of SP1. In addition, enhanced cell migration was remarkably reversed by ITGA2 depletion or p-AKT inhibitor treatment. Conclusion: This study clarified the mechanism of PSAT1 in promoting ER-negative breast cancer metastasis, which may provide mechanistic clues for attenuating breast cancer metastasis.

Breast cancer progression is closely linked to immune cells within the tumor microenvironment (TME), but the immune landscape differences across HER2-positive (HER2+), triple-negative (TNBC), and ER-positive (ER+) subtypes have yet to be systematically characterized. In this study, we characterized immune landscape differences across HER2-positive (HER2+), triple-negative (TNBC), and ER-positive (ER+) breast cancers using single-cell RNA sequencing data, focusing on T cells, macrophages, and B cells. Our analysis revealed that cytotoxic CD8 + T cells were more abundant in TNBC but showed signs of dysfunction. Macrophage subsets, including an NDUFB8 + population, exhibited divergent functional orientations across subtypes. B cells in TNBC exhibited functional alterations, characterized by a decreased proportion of plasmablasts and an increased proportion of memory B cells. Single-cell regulatory network inference and clustering (SCENIC) analysis predicted a set of subtype-specific candidate transcription factors (TFs), including E2F8 across all subtypes and ATF7 in HER2 + tumors, whose activity correlated with clinical outcomes. Finally, mapping multicellular communication networks revealed both conserved and subtype-specific signaling pathways. Together, these results present a detailed transcriptional landscape of immune heterogeneity in breast cancer and contribute novel insights that may inform the design of subtype-specific immunotherapies.