Anxa2 binds to STAT3 and promotes epithelial to mesenchymal transition in breast cancer cells

Abstract

Overexpression of annexin A2 (Anxa2) is correlated with invasion and metastasis in breast cancer cells. In this study, breast cancer patients with upregulated Anxa2 exhibited poor overall and disease-free survival rates. Anxa2 expression was also positively correlated with the expression of epidermal growth factor receptor (EGFR) and epithelial-mesenchymal transition (EMT) markers in breast cancer tissues and cell lines. Moreover, knockdown of Anxa2 impaired EGF-induced EMT, as well as the migration and invasion of breast cancer cells in vitro. Meanwhile, Anxa2 depletion significantly ablated pulmonary metastasis in a severe combined immunodeficiency mouse model of breast cancer. Importantly, Anxa2 reduction inhibited EGF-induced activation of STAT3, which is required for EGF-induced EMT. Anxa2 directly bound to STAT3 and enhanced its transcriptional activity, thereby indicating that Anxa2 promotes EGF-induced EMT in a STAT3-dependent manner. Our findings provide clinical evidence that Anxa2 is a poor prognostic factor for breast cancer and reveal a novel mechanism through which Anxa2 promotes breast cancer metastasis.