Abstract
BackgroundDKK1 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.MethodsWestern 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.ResultsDKK1 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.ConclusionsDKK1 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.
Highlights
DKK1 has been reported to act as a tumor suppressor in breast cancer
Knockdown of DKK1 in MCF-7 and MDAMB-231 cells enhanced cells migration and invasion using wound scratch assay and transwell assay (Fig. 3). These results indicated that DKK1 play an inhibitory role in breast cancer cells migration and invasion in vitro
In order to confirm that matrix metalloproteinase 7 (MMP7) was one of the dominant downstream effector of β-catenin, we explored whether the effect of XAV-939, an inhibitor of β-catenin accumulation could reverse MMP7 expression induced by DKK1 knockdown
Summary
DKK1 has been reported to act as a tumor suppressor in breast cancer. The mechanism of DKK1 inhibits breast cancer migration and invasion was still unclear. Some studies have suggested that DKK1 acts as a putative tumor suppressor in breast cancer [9, 10]. The mechanism of DKK1 inhibits breast cancer metastasis was still unclear. Its expression was associated with poor prognosis in tumors of the pancreas, colon, brain and breast cancers [13,14,15]. To our knowledge, it remains unclear whether DKK1 inhibits breast cancer metastasis through suppression of MMP-7 expression. Our results suggested DKK1 inhibited migration and invasion by suppression
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