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Proc Natl Acad Sci U S A. 2013 Oct 8;110(41):E3937-44. doi: 10.1073/pnas.1315022110. Epub 2013 Sep 25.

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

Author information

1
Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720.

Abstract

The protein 14-3-3σ (stratifin) is frequently described as a tumor suppressor silenced in about 80% of breast tumors. Intriguingly, we show that 14-3-3σ 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 14-3-3σ 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/14-3-3σ complex and cellular migration are regulated by PKCζ-dependent phosphorylation, a finding that could form the basis for intervention in aggressive breast carcinomas expressing 14-3-3σ. Our data suggest that the biology of this protein is important in cellular movement and is contingent on breast cancer subtype.

KEYWORDS:

14-3-3 family; basal breast cancer; cytoskeleton; motility; triple-negative

PMID:
24067649
PMCID:
PMC3799319
DOI:
10.1073/pnas.1315022110
[Indexed for MEDLINE]
Free PMC Article

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