14-3-3σ stabilizes a complex of soluble actin and intermediate filament to enable breast tumor invasion

The protein 14-3-3s (stratifin) is frequently described as a tumor suppressor silenced in about 80% of breast tumors. Intriguingly, we show that 14-3-3s expression, which in normal breast is localized to the myoepithelial cells, tracks with malignant phenotype in two models of basal-like breast cancer progression, and in patients, it is associated with basal-like subtype and poor clinical outcome. We characterized a mechanism by which 14-3-3s guides breast tumor invasion by integrating cytoskeletal dynamics: it stabilizes a complex of solubilized actin and intermediate filaments to maintain a pool of "bioavailable"complexes for polarized assembly during migration. We show that formation of the actin/cytokeratin/ 14-3-3s complex and cellular migration are regulated by PKC.dependent phosphorylation, a finding that could form the basis for intervention in aggressive breast carcinomas expressing 14-33s. Our data suggest that the biology of this protein is important in cellular movement and is contingent on breast cancer subtype.