SLC39A4 induces EMT and promotes triple-negative breast cancer cell proliferation and migration by activating ERK signaling

Solute carrier family 39 member 4 (SLC39A4) has been reported as a proto-oncogene activated in various cancers. however, its role in breast cancer is unclear. Our study found that the expression of SLC39A4 is up-regulated in breast cancer, especially in basal-like subtype. High expression of SLC39A4 significantly correlated with a higher T stage, N stage, as well as shorter recurrence-free survival (RFS) and overall survival (OS). Total intracellular zinc ion content in SLC39A4 over-expression group was significantly higher than that in the control group by inductively coupled plasma-mass spectrometry (ICP-MS). Knockdown of SLC39A4 significantly inhibited TNBC cell proliferation, colony formation, migration and invasion. Mechanistically, the result of RNA sequencing (RNA-seq) and KEGG enrichment analysis suggest that knockdown of SLC39A4 affect MAPK signaling pathways in triple-negative breast cancer (TNBC) cell. We further confirm that SLC39A4 promotes TNBC cell proliferation and migration by activating ERK phosphorylation. Interestingly, SLC39A4 induces the epithelial-to-mesenchymal transition (EMT) and can be reversed by ERK inhibitor. In addition, SLC39A4 expression in basal-like breast cancer was negatively correlated with infiltrating levels of CD8 + T cell, Macrophages, Neutrophils and Dendritic Cells, and was also negatively associated with the expression of immune checkpoint PD1 and PDL1. In summary, SLC39A4 induces the EMT and promotes proliferation and migration via the ERK signaling pathway in TNBC cells. SLC39A4 can serve as a novel predictive biomarker for prognosis and immune infiltration in TNBC.