Activation of major vault protein by TGF-beta is associated with advanced malignancy and poor prognosis in breast cancer

Emerging studies have demonstrated that major vault protein (MVP) may play critical roles in tumor development and progression. However, the biology functions of MVP in breast cancer have not yet been evaluated. The present study is to investigate the expression level and the significance of MVP in breast cancer and to explore the mechanism underlying the deregulation of MVP. We examined the expression of MVP and the relationship with clinicopathological features. Cell proliferation and transwell assays were performed to explore the effect of MVP in breast cancer cell lines. The results indicated that the expression levels of MVP mRNA and protein were significantly higher in breast cancer tissues and the overexpression of MVP was associated with lymph node invasion and advanced tumor stage. We also identified that MVP could be an independent prognostic factor. In addition, knockdown of MVP showed that deficiency of MVP retarded cell growth and invasion ability. Furthermore, we noticed that TGF-β signaling activation was involved in regulating MVP expression as MVP expression could be reduced by TGF-β signaling inhibitor. In conclusion, we found that abnormal activation of TGF-β signaling could induce MVP expression and high expression level of MVP promoted breast cancer cells proliferation and invasion, indicating that MVP could serve as a potential target for therapy of breast cancer.