SNCA inhibits epithelial-mesenchymal transition and correlates to favorable prognosis of breast cancer

Abstract

Alpha-synuclein (SNCA) is a pathological hallmark of Parkinson's disease, known to be involved in cancer occurrence and development; however, its specific effects in breast cancer remain unknown. Data from 150 patients with breast cancer were retrieved from tissue microarray and analyzed for SNCA protein level using immunohistochemistry. Functional enrichment analysis was performed to investigate the potential role of SNCA in breast cancer. SNCA-mediated inhibition of epithelial-mesenchymal transition (EMT) was confirmed with western blotting. The effects of SNCA on invasion and migration were evaluated using transwell and wound-healing experiments. Furthermore, the potential influence of SNCA expression level on drug sensitivity and tumor infiltration by immune cells was analyzed using the public databases. SNCA is lowly expressed in breast cancer tissues. Besides, in vitro and in vivo experiments, SNCA overexpression blocked EMT and metastasis, and the knockdown of SNCA resulted in the opposite effect. A mouse model of metastasis verified the restriction of metastatic ability in vivo. Further analysis revealed that SNCA enhances sensitivity to commonly used anti-breast tumor drugs and immune cell infiltration. SNCA blocks EMT and metastasis in breast cancer and its expression levels could be useful in predicting the chemosensitivity and evaluating the immune microenvironment in breast cancer.