Formin-like
protein 2 (FMNL2) belongs to a highly conserved family of cytoskeletal remodeling
proteins that have been reported to be implicated in various actin-dependent physiological and
cancer-associated processes. In this study, we mainly investigated the effects of FMNL2 on
breast cancer cell migration and invasion, and the underlying mechanisms involved. We found that FMNL2 reduced cell migration and invasion of
breast cancer in vitro and in vivo. Further, FMNL2 disrupted actin cytoskeleton rearrangement and hampered the RhoA/LIMK/
Cofilin pathway in
breast cancer cells. Critically, both Rho inhibitor ZOL and LIMK inhibitor BMS3 significantly abrogated these migration-promoting effects in FMNL2-silencing MDA-MB-231 and BT549 cells. RhoA/LIMK/
Cofilin pathway was involved in FMNL2 silencing-induced actin cytoskeleton rearrangement in MDA-MB-231 and BT549 cells. More importantly, cytoplasmic p27 promoted FMNL2-mediated cell migration and invasion through RhoA/LIMK/
Cofilin pathway in MCF7 and MDA-MB-231 cells. In addition, the expression and prognosis of FMNL2 were associated with ER in
breast cancer. Furthermore, ERĪ± overexpression reduced the
protein levels of FMNL2 in
breast cancer cells, which were reversed by
MG132. In conclusion, FMNL2 suppressed cell migration and invasion of
breast cancer by inhibiting RhoA/LIMK/
Cofilin pathway through a reduction of cytoplasmic p27. This finding implies that the interference of FMNL2-mediated RhoA/LIMK/
Cofilin pathway involving the cytoplasmic p27 may be a promising strategy for ameliorating
breast cancer metastasis and prognosis.