Diaphanous-related formin-3 overexpression inhibits the migration and invasion of triple-negative breast cancer by inhibiting RhoA-GTP expression

Abstract

Triple-negative breast cancer (TNBC) is associated with a high risk of metastasis, recurrence, and poor prognosis. TNBC is insensitive to existing endocrine and targeted breast cancer therapies because it lacks the expression of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2. Therefore, there is an urgent need for identifying novel targets to improve the efficacy of TNBC treatment. Diaphanous-related formin-3 (DIAPH3) regulates cytoskeleton formation to regulate cell adhesion, migration, and differentiation. A previous study showed that DIAPH3 promoted the metastasis of prostate cancer. However, DIAPH3 expression in TNBC and its effect on TNBC development have not been reported to date. In present study, we investigated the expression and functions of DIAPH3 in TNBC. Results of immunohistochemical staining showed that DIAPH3 expression significantly decreased in breast cancer tissues, especially TNBC tissues, compared with that in paired non-tumor tissues. In addition, DIAPH3 expression was associated with TNM stage and lymph node metastasis, but not with tumor size in patients with TNBC. Further, DIAPH3 overexpression clearly suppressed the migration and invasion of MDA-MB-231 cells and decreased the expression of Ras Homolog Family Member A (RhoA), RhoA-GTP, Matrix Metallopeptidase 2 (MMP-2), and MMP-9. Thus, we predict that DIAPH3 overexpression inhibits the migration and invasion of TNBC by inhibiting RhoA-GTP expression and the results of the present study provide new insights for developing DIAPH3-targeting therapies for TNBC.