Background: DKK1 has been reported to act as a tumor suppressor in breast cancer. However, the mechanism of DKK1 inhibits breast cancer migration and invasion was still unclear.
Methods: Western blot and real time PCR was used to detect the expression of DKK1, β-catenin and MMP7 in breast cancer cells. Wound scratch assay and transwell assay was employed to examine migration and invasion of breast cancer cell.
Results: DKK1 overexpression dramatically inhibits breast cancer cell migration and invasion. Knockdown of DKK1 promotes migration and invasion of breast cancer cells. DKK1 suppressed breast cancer cell migration and invasion through suppression of β-catenin and MMP7 expression. XAV-939, an inhibitor of β-catenin accumulation could reverse DKK1 silencing-induced MMP7 expression in breast cancer cells. Meanwhile, XAV-939 also could reverse the increase in the cell number invaded through Matrigel when DKK1 was knockdown. Furthermore, depletion of MMP7 also could reverse DKK1 knockdown-induced increase in the cell number invaded through Matrigel.
Conclusions: DKK1 inhibits migration and invasion of breast cancer cell through suppression of β-catenin/MMP7 pathway, our findings offered a potential alternative for breast cancer prevention and treatment.
Keywords: Breast cancer; DKK1; MMP7; Migration and invasion; β-Catenin.