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

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 ahighly invasivebasal- likebreast cancer subtypeboth in apanel of human breast cancer cell lines as in breast cancer patients and that AnxA1 is functionally related to breast cancer progression. AnxA1 knockdownininvasivebasal- likebreast cancer cells reduced the number of spontaneous lung metastasis, whereas additional expression of AnxA1 enhanced metastatic spread. AnxA1 promotes metastasis formation by enhancingTGF beta/Smad signalingandactin reorganization, which facilitates an EMT-like switch, thereby allowing ef. cient cell migration and invasion of metastatic breast cancer cells.Molecular tumour pathology - and tumour genetic

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