Matrix metalloproteinase-2 regulates MDA-MB-231 breast cancer cell invasion induced by active mammalian diaphanous-related formin 1

Abstract

Mammalian diaphanous-related formin 1 (mDia1) was initially identified as a Rho GTPase effector involved in the progression of various diseases, including types of cancer. However, the precise underlying molecular mechanism of mDia1-mediated cancer cell invasion remains to be elucidated. In the present study, mDia1 expression was demonstrated to be upregulated in tissues from a number of cancer types, including kidney, prostate, and breast cancer using immunohistochemical analysis. Forced expression of a constitutively active (CA) form of mDia1 induces invasion, as measured by Transwell invasion assay, of MDA-MB-231 cells, which is a highly invasive breast cancer cell line, and this effect was markedly impaired by matrix metalloproteinase (MMP)-2 silencing. Furthermore, the present study demonstrated that overexpression of the CA form of mDia1 leads to the induction of invasive ability in MCF-7 cells, which is a non-invasive breast cancer cell line, as a result of increased MMP-2 activity. Thus, the results of the current study suggest that mDia1 is an important regulator of breast cancer cell invasion and that this effect may be mediated by MMP-2 activity.