Previous studies report the upregulation of the secretory Rab27B small GTPase in human breast cancer, which could promote invasive growth and metastasis in estrogen receptor (ER)-positive breast cancer cells. However, there is limited evidence for its role in ER-negative breast cancer, along with the signaling pathways. Consistent with previous studies, we here confirmed that Rab27B is upregulated in breast tumor tissue in comparison with normal breast tissue. In addition, in ER-negative breast cancer cell line MDA-MB-231, when the levels of Rab27B expression were further elevated by transduction with recombinant lentivirus vector, migration and invasion assays demonstrated that cell migration and invasion was significantly stimulated. Moreover, Rab27B overexpression increased levels of β-catenin, followed by upregulation of vascular endothelial growth factor (VEGF). Our findings reveal a key function for the Rab27B-mediated modulation of β-catenin and VEGF in ER-negative breast cancer cell metastasis. Notably, the suppressed expression of Rab27B, β-catenin and VEGF was found in calycosin-treated MDA-MB-231 cells, accompanied with decreased invasive and migratory potential of these cells. What's more, these inhibitory effects of calycosin were all attenuated by Rab27B overexpression. The results demonstrated that calycosin-induced inhibition of migration and invasion in ER-negative breast cancer cells may be associated with the inactivation of Rab27B-dependent signaling, and suggest that antagonism of this pathway by calycosin may offer alternative therapeutic strategy for the aggressive breast cancer.
Keywords: Breast cancer; Calycosin; Invasion; Migration; Phytoestrogens; Rab27B.
Copyright © 2019. Published by Elsevier B.V.