title: 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.
authors: Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, The Key Laboratory of Breast Cancer Prevention and Therapy, Ministry of Education, Key Laboratory of Cancer Prevention and Therapy, Tianjin, PR China.
authors: Tong
authors: T
authors: Wang
authors: Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, The Key Laboratory of Breast Cancer Prevention and Therapy, Ministry of Education, Key Laboratory of Cancer Prevention and Therapy, Tianjin, PR China.
authors: Jie
authors: J
authors: Yuan
authors: Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, The Key Laboratory of Breast Cancer Prevention and Therapy, Ministry of Education, Key Laboratory of Cancer Prevention and Therapy, Tianjin, PR China.
authors: Jie
authors: J
authors: Zhang
authors: Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, The Key Laboratory of Breast Cancer Prevention and Therapy, Ministry of Education, Key Laboratory of Cancer Prevention and Therapy, Tianjin, PR China.
authors: Ran
authors: R
authors: Tian
authors: Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, The Key Laboratory of Breast Cancer Prevention and Therapy, Ministry of Education, Key Laboratory of Cancer Prevention and Therapy, Tianjin, PR China.
authors: Wei
authors: W
authors: Ji
authors: Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, The Key Laboratory of Breast Cancer Prevention and Therapy, Ministry of Education, Key Laboratory of Cancer Prevention and Therapy, Tianjin, PR China.
authors: Yan
authors: Y
authors: Zhou
authors: Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, The Key Laboratory of Breast Cancer Prevention and Therapy, Ministry of Education, Key Laboratory of Cancer Prevention and Therapy, Tianjin, PR China.
authors: Yi
authors: Y
authors: Yang
authors: Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, The Key Laboratory of Breast Cancer Prevention and Therapy, Ministry of Education, Key Laboratory of Cancer Prevention and Therapy, Tianjin, PR China.
authors: Weijie
authors: W
authors: Song
authors: Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, The Key Laboratory of Breast Cancer Prevention and Therapy, Ministry of Education, Key Laboratory of Cancer Prevention and Therapy, Tianjin, PR China.
authors: Fei
authors: F
authors: Zhang
authors: Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, The Key Laboratory of Breast Cancer Prevention and Therapy, Ministry of Education, Key Laboratory of Cancer Prevention and Therapy, Tianjin, PR China.
authors: Ruifang
authors: R
authors: Niu
mesh_terms: D000328:Adult; D000818:Animals; D017306:Annexin A2 / Q000235:genetics / Q000378:metabolism*; D017209:Apoptosis; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D049109:Cell Proliferation; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D047468:Immunoprecipitation; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism / Q000556:secondary*; D051379:Mice; D016513:Mice, SCID; D009367:Neoplasm Staging; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D014407:Tumor Cells, Cultured; D014945:Wound Healing; D023041:Xenograft Model Antitumor Assays
chemical_list: C472822:ANXA2 protein, human; D017306:Annexin A2; D012333:RNA, Messenger; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human
keywords: Anxa2; breast cancer; epidermal growth factor receptor; epithelial–mesenchymal transition