Tim-3 promotes cell aggressiveness and paclitaxel resistance through NF-κB/STAT3 signalling pathway in breast cancer cells.

OBJECTIVE

Although T-cell immunoglobulin and mucin-domain containing molecule-3 (Tim-3) has been recognized as a promising target for cancer immunotherapy, its exact role in breast cancer has not been fully elucidated.

METHODS

gene expression in breast cancer and its prognostic significance were analyzed. Associated mechanisms were then explored by establishing Tim-3-overexpressing breast cancer cells.

RESULTS

In a pooled analysis of The Cancer Genome Atlas (TCGA) database, gene expression levels were significantly higher (P<0.001) in breast cancer tissue, compared with normal tissues. Tim-3 was a prognosis indicator in breast cancer patients [relapse-free survival (RFS), P=0.004; overall survival (OS), P=0.099]. Tim-3 overexpression in Tim-3 breast cancer cells promoted aggressiveness of breast cancer cells, as evidenced by enhanced proliferation, migration, invasion, tight junction deterioration and tumor-associated tubal formation. Tim-3 also enhanced cellular resistance to paclitaxel. Furthermore, Tim-3 exerted its function by activating the NF-κB/STAT3 signalling pathway and by regulating gene expression [cyclin D1 (), , matrix metalloproteinase-1(), , vascular endothelial growth factor () upregulation, concomitant with downregulation). Lastly, Tim-3 downregulated tight junction-associated molecules zona occludens (ZO)-2, ZO-1 and occludin, which may further facilitate tumor progression.

CONCLUSIONS

Tim-3 plays an oncogenic role in breast cancer and may represent a potential target for antitumor therapy.