Anxa2 binds to STAT3 and promotes epithelial to mesenchymal transition in breast cancer cells.
Anxa2 binds to STAT3 and promotes epithelial to mesenchymal transition in breast cancer cells.
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Anxa2 与 STAT3 结合并促进乳腺癌细胞上皮细胞向间质细胞的转变
DOI：
10.18632/oncotarget.5199
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发表时间：
2015-10-13
期刊：
影响因子：
--
通讯作者：
Niu R
中科院分区：
文献类型：
--
作者：
Wang T;Yuan J;Zhang J;Tian R;Ji W;Zhou Y;Yang Y;Song W;Zhang F;Niu R
Annexin A2（Anxa2）的过表达与乳腺癌细胞的侵袭和转移相关。在这项研究中，Anxa2上调的乳腺癌患者表现出较差的总体和无病生存率。在乳腺癌组织和细胞系中，Anxa2的表达与表皮生长因子受体（EGFR）和上皮间质转化（EMT）标志物的表达也呈正相关。此外，Anxa2的敲低损害EGF诱导的EMT，以及体外乳腺癌细胞的迁移和侵袭。同时，Anxa2耗竭显著消融了乳腺癌严重联合免疫缺陷小鼠模型中的肺转移。重要的是，Anxa 2的减少抑制了EGF诱导的STAT 3激活，而这是EGF诱导的EMT所需的。Anxa2直接与STAT3结合并增强其转录活性，从而表明Anxa2以STAT3依赖的方式促进EGF诱导的EMT。我们的研究结果提供了临床证据，Anxa2是乳腺癌的预后不良因素，并揭示了Anxa2促进乳腺癌转移的新机制。
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.