论文部分内容阅读
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: Tim-3 gene expression in breast cancer and its prognostic significance were analyzed.Associated mechanisms were then explored in vitro by establishing Tim-3-overexpressing breast cancer cells.Resuits: In a pooled analysis of The Cancer Genome Arias (TCGA) database,Tim-3 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-3low 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 (CCND1),C-Myc,matrix metalloproteinase-l(MMP1),TWIST,vascular endothelial growth factor (VEGF) upregulation,concomitant with Ecadherin downregulation).Lastly,Tim-3 downregnlated 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.