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    Proc Natl Acad Sci U S A. 2010 Apr 6;107(14):6340-5. Epub 2010 Mar 22.

    Annexin A1 regulates TGF-beta signaling and promotes metastasis formation of basal-like breast cancer cells.

    de Graauw M, van Miltenburg MH, Schmidt MK, Pont C, Lalai R, Kartopawiro J, Pardali E, Le Dévédec SE, Smit VT, van der Wal A, Van't Veer LJ, Cleton-Jansen AM, ten Dijke P, van de Water B.

    Source

    Division of Toxicology, Leiden/Amsterdam Center for Drug Research, Leiden University, 2300 RA, Leiden, The Netherlands.

    Abstract

    Annexin A1 (AnxA1) is a candidate regulator of the epithelial- to mesenchymal (EMT)-like phenotypic switch, a pivotal event in breast cancer progression. We show here that AnxA1 expression is associated with a highly invasive basal-like breast cancer subtype both in a panel of human breast cancer cell lines as in breast cancer patients and that AnxA1 is functionally related to breast cancer progression. AnxA1 knockdown in invasive basal-like breast cancer cells reduced the number of spontaneous lung metastasis, whereas additional expression of AnxA1 enhanced metastatic spread. AnxA1 promotes metastasis formation by enhancing TGFbeta/Smad signaling and actin reorganization, which facilitates an EMT-like switch, thereby allowing efficient cell migration and invasion of metastatic breast cancer cells.

    PMID:
    20308542
    [PubMed - indexed for MEDLINE]
    PMCID: PMC2852023
    Free PMC Article

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