Knockdown of flotillin-2 impairs the proliferation of breast cancer cells through modulation of Akt/FOXO signaling

Lipid rafts, specialized domains in cell membranes, function as physical platforms for various molecules to coor- dinate a variety of signal transduction processes. Flotillin-2 (FLOT2), a marker of lipid rafts, is involved in the progres- sion of cancer, yet the precise mechanismremains unclear. In the present study, we examined the effect of FLOT2 on cell proliferation and found that silencing endogenous FLOT2 with shRNAs inhibited proliferation of breast cancer cells. Furthermore, the antiproliferative effect of silencing FLOT2 on breast cancer cells was associated with upregulation of cyclin-dependent kinase( CDK) inhibitorsp21 Cip1 and p27 Kip1 . Moreover, we further demonstrated that the silencing of FLOT2 enhanced the transcriptional activity of FOXO factors by decreasing its phosphorylation through inhibiting the PI3K/Akt signaling pathway. Taken together, our results provide the first demonstration of a novel mechanism by which FLOT2 induces proliferation of breast cancer cells, and our findings suggest that FLOT2 plays an important role in onco- genesis of breast cancer and thereby may be a potential target for human breast cancer treatment.