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About 70\u201075% of primary breast cancers belong to estrogen receptor (ER)\u2010positive breast cancer. In the development of ER\u2010positive breast cancer, abnormal activation of the ER\u03b1 pathway plays an important role and is also a key point leading to the failure of clinical endocrine therapy. In this study, we found that the small molecule peptide chlorotoxin (CTX) can significantly inhibit the proliferation, migration and invasion of breast cancer cells. In in vitro study, CTX inhibits the expression of ER\u03b1 in breast cancer cells. Further studies showed that CTX can directly bind to ER\u03b1 and change the protein secondary structure of its LBD domain, thereby inhibiting the ER\u03b1 signaling pathway. In addition, we also found that vasodilator stimulated phosphoprotein (VASP) is a target gene of ER\u03b1 signaling pathway, and CTX can inhibit breast cancer cell proliferation, migration, and invasion through ER\u03b1\/VASP signaling pathway. In in vivo study, CTX significantly inhibits growth of ER overexpressing breast tumor and, more importantly, based on the mechanism of CTX interacting with ER\u03b1, we found that CTX can target ER overexpressing breast tumors in vivo. Our study reveals a new mechanism of CTX anti\u2010ER\u2010positive breast cancer, which also provides an important reference for the study of CTX anti\u2010ER\u2010related tumors.<\/jats:p>","DOI":"10.1002\/cam4.2019","type":"journal-article","created":{"date-parts":[[2019,2,26]],"date-time":"2019-02-26T06:56:13Z","timestamp":1551164173000},"page":"1679-1693","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Chlorotoxin targets ER\u03b1\/VASP signaling pathway to combat breast cancer"],"prefix":"10.1002","volume":"8","author":[{"given":"Ying","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Pathology and Pathophysiology, Hubei Provincial Key Laboratory of Developmentally Originated Disease, School of Basic Medical Sciences Wuhan University Wuhan Hubei China"},{"name":"Department of Oncology Xiangyang No.1 People\u2019s Hospital, Hubei University of Medicine Xiangyang Hubei 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