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

Abstract

Significance We characterize a mechanism by which 14-3-3σ directs cell migration and tumor invasion through regulating cytoskeletal solubility and dynamics. Our data suggest that 14-3-3σ expression, rather than being a tumor suppressor, in fact, aids in breast tumor invasion at least in a subset of carcinomas. Our findings warrant further investigation into the role of this molecule in normal mammary gland and breast tumors and, indeed, in epithelial tissues and tumors where 14-3-3σ is expressed.

Post-translational modifications of intermediate filament proteins: mechanisms and functions

“…The role of keratin binding to 14-3-3 proteins in modulating mitosis progression likely involves other pathways, including keratin phosphorylation-mediated regulation of Raf-1 binding to 14-3-3 (Ku et al J Cell Biol 2004), cdc25 binding to 14-3-3 (Margolis et al, Cell 2006) and the nuclear distribution of the 14-3-3zeta protein. Additionally, 14-3-3 promotes mammary tumorigenesis by stabilizing a soluble K5–K17–actin complex; this function of 14-3-3 is dependent on PKCζ phosphorylation 77 . Maintenance of this complex is thought to facilitate polarized cytoskeletal filament assembly during cell migration.…”

Intermediate filaments in cell migration and invasion: the unusual suspects

“…Unlike vimentin, keratin filaments are not sensitive to microtubule depolymerization and appear mainly controlled by actin [12]. The tumor suppressor protein 14-3-3s forms a complex with solubilized actin and keratins 5 and 17, facilitating their polarized assembly during migration and invasion of breast tumor cells [45]. However, vimentin filaments were recently shown to interact with myosinIIB [39 ], which may explain why in absence of microtubules the vimentin network is remodeled in an actin-dependent manner [46].…”

Long non‑coding RNA HOX transcript antisense RNA promotes expression of 14‑3‑3σ in non‑small cell lung cancer

“…Future studies by our group will focus on the potential effects of HOTAIR on the expression of 14-3-3 β, γ and θ, as inhibition of HOTAIR may be an effective way of inhibiting the expression of 14-3-3σ and other 14-3-3 proteins. In addition, as overexpression of HOTAIR and 14-3-3 protein has been detected in pancreatic cancer, lung adenocarcinoma and breast tumor (8,9,10) and correlates with more aggressive tumors and poor prognosis (11,24,25), further studies investigating the association between HOTAIR and 14-3-3 proteins in other types of cancer are warranted.…”

“…This is important, as enhanced cell proliferation and survival are key characteristics of cancer cells (7). Overexpression of 14-3-3 proteins has been detected in many types of human cancer such as pancreatic cancer (8), lung adenocarcinoma (9), breast tumor (10) and is correlated with more aggressive tumors and poor prognosis (10,11). In lung cancer, it has been demonstrated that the 14-3-3 isoforms β, γ, σ and θ are overexpressed in tumor tissue compared with normal tissues (4,12).…”