Long-term cadmium exposure promoted breast cancer cell migration and invasion by up-regulating TGIF

Abstract

Cadmium (Cd) is a known human carcinogen. Previous studies have demonstrated that Cd exposure promoted migration and invasion of breast cancer cells. However, the molecular mechanisms underlying this process have not yet been clearly addressed. The purpose of this study was to investigate whether TG-interacting factor (TGIF) was involved in long-term Cd exposure-induced migration and invasion of breast cancer cells. Human breast cancer cells were continuously exposed to Cd for eight weeks. Western blot and qRT-PCR assays were performed to measure the expression of protein and mRNA. Migration and invasion assays were performed to assess the migratory and invasive ability of human breast cancer cells. Our data indicated that long-term Cd exposure obviously increased the expression of TGIF protein and mRNA in human breast cancer cells. Long-term Cd exposure increased the ability of migration and invasion of human breast cancer cells, which could be inhibited by transfection of small interfering RNA (siRNA) targeting TGIF. We also observed that the long-term Cd exposure-induced up-regulation of MMP2 mRNA expression was modulated by TGIF. In conclusion, our findings suggested that TGIF/MMP2 signaling axis might be involved in malignant progression stimulated by long-term Cd exposure in human breast cancer.