Chlorotoxin targets ERα/VASP signaling pathway to combat breast cancer

Cancer Medicine
Ying WangLei Wei

Abstract

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 stu...Continue Reading

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Citations

Dec 5, 2020·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Sepideh MirzaeiManoj Garg

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Methods Mentioned

BETA
PCR
Protein Assay
electrophoresis
pull‐down
immunoprecipitation
ChIP
transfection
fluorescence
circular dichroism
xenografts

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