Open AccessChlorotoxin targets ERα/VASP signaling pathway to combat breast cancer
Author(s) -
Wang Ying,
Li Kai,
Han Song,
Tian Yihao,
Hu Pengchao,
Xu Xiaolong,
He Yanqi,
Pan Wenting,
Gao Yang,
Zhang Zun,
Zhang Jingwei,
Wei Lei
Publication year - 2019
Publication title -
cancer medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 53
ISSN - 2045-7634
DOI - 10.1002/cam4.2019
Subject(s) - breast cancer , cancer research , estrogen receptor , cancer , signal transduction , cell growth , estrogen receptor alpha , metastasis , biology , medicine , chemistry , microbiology and biotechnology , biochemistry
Breast cancer is one of the most common malignant tumors among women worldwide. About 70‐75% of primary breast cancers belong to estrogen receptor (ER)‐positive breast cancer. In the development of ER‐positive breast cancer, abnormal activation of the ERα 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 ERα in breast cancer cells. Further studies showed that CTX can directly bind to ERα and change the protein secondary structure of its LBD domain, thereby inhibiting the ERα signaling pathway. In addition, we also found that vasodilator stimulated phosphoprotein (VASP) is a target gene of ERα signaling pathway, and CTX can inhibit breast cancer cell proliferation, migration, and invasion through ERα/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 ERα, we found that CTX can target ER overexpressing breast tumors in vivo. Our study reveals a new mechanism of CTX anti‐ER‐positive breast cancer, which also provides an important reference for the study of CTX anti‐ER‐related tumors.