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

被引：79

作者：

Wang, Tong ^{[1
]}

Yuan, Jie ^{[1
]}

Zhang, Jie ^{[1
]}

Tian, Ran ^{[1
]}

Ji, Wei ^{[1
]}

Zhou, Yan ^{[1
]}

Yang, Yi ^{[1
]}

Song, Weijie ^{[1
]}

Zhang, Fei ^{[1
]}

Niu, Ruifang ^{[1
]}

机构：

[1] Tianjin Med Univ, Canc Inst & Hosp, Natl Clin Res Ctr Canc,Key Lab Canc Prevent & The, Key Lab Breast Canc Prevent & Therapy,Minist Educ, Tianjin, Peoples R China

来源：

ONCOTARGET | 2015年 / 6卷 / 31期

基金：

中国国家自然科学基金;

关键词：

Anxa2; breast cancer; epithelial-mesenchymal transition; epidermal growth factor receptor; GROWTH-FACTOR; ANNEXIN-II; SIGNAL TRANSDUCER; UP-REGULATION; INVASION; ACTIVATOR; PHOSPHORYLATION; PROLIFERATION; A2; TRANSCRIPTION-3;

D O I：

10.18632/oncotarget.5199

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：30975 / 30992

页数：18

共 48 条

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