Lunasin suppresses the migration and invasion of breast cancer cells by inhibiting matrix metalloproteinase-2/-9 via the FAK/Akt/ERK and NF-κB signaling pathways

Lunasin is a naturally existing bioactive peptide with an Arg-Gly-Asp (RGD) motif, which competes with integrins to bind with the extracellular matrix (ECM) consequently suppressing the integrin-mediated signaling pathway. Owing to the RGD motif, lunasin has been proven as an effective anti-inflammatory, antitumor and antimetastatic agent in many types of cancer. However, knowledge of its inhibitory effect on metastasis and the related mechanism of action in breast cancer cells is limited. In this study, the inhibitory effect of lunasin on the proliferation, migration and invasion of two typical breast cancer cell lines, ER-negative MDA-MB-231 with αVβ3 expression and ER-positive MCF-7 with αVβ5/α5β1 expression, were examined in vitro as well the related mechanisms. The results demonstrated that lunasin (10-20 µM) effectively inhibited the migration and invasion activity and expression of matrix metalloproteinase (MMP)‑2/-9 in both breast cancer cell lines. Meanwhile, we also found that lunasin inhibited the phosphorylation of focal adhesion kinase (FAK), Src, Akt, ERK and nucleus translocation of NF-κB, which indicates that, possibly via competing with αVβ3 or αVβ5/α5β1 integrin, lunasin suppresses the metastasis of breast cancer cells through integrin-mediated FAK/Akt/ERK and NF-κB signaling pathways followed by downregulation of the activity and expression of MMP-2/-9.