Serum amyloid A1 promote progression of breast cancer and is associated with epithelial-mesenchymal transition.

Serum amyloid A1 (SAA1) is closely associated with malignant progression and unfavorable prognosis in multiple cancers. However, the specific cellular sources and mechanisms of SAA1 within the breast cancer tumor microenvironment (TME) remain incompletely understood. This study aims to investigate the SAA1 expression in the breast cancer and to elucidate its functional roles in tumor progression. We integrated 17 single-cell RNA sequencing (scRNA-seq) and 148 bulk RNA sequencing (bulk RNA-seq) data of breast cancer tissues. We identified SAA1+ cell clusters in TME, revealing significant interactions between SAA1+ cells and others. Pseudotime trajectory analysis revealed dynamic transcriptional regulation during SAA1+ cell differentiation. Co-cultured cell and subcutaneous tumor model investigated the potential mechanism of SAA1. SAA1 was highly expressed in cancer-associated fibroblasts (CAFs) and tumor cells within TME. Highly SAA1 expression and increased CAFs infiltration were associated with poor prognosis for breast cancer patients. Subcutaneous tumor co-culture experiments further demonstrated that SAA1-overexpressing CAFs promote tumor proliferation. Cellular trajectory analysis indicated that SAA1 enhanced the invasive and migratory capacities of breast cancer cells and induced activation of the epithelial-mesenchymal transition (EMT) pathway, characterized by upregulation of vimentin (VIM) and collagen type I alpha 1 (COL1A1) and downregulation of CDH1. Ligand-receptor interaction analysis suggested that SAA1+ cells may exert their biological effects within the TME through activation of the pleiotrophin (PTN) signaling pathway. SAA1 is expressed in both CAFs and tumor cells within the breast cancer. High expression of SAA1 promotes malignant progression and induces the EMT process. This effect may be closely associated with the activation of the PTN signaling pathway.