Chlorotoxin targets ERα/VASP signaling pathway to combat breast cancer

Cancer Med. 2019 Apr;8(4):1679-1693. doi: 10.1002/cam4.2019. Epub 2019 Feb 25.


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.

Keywords: ERα; VASP; breast cancer; chlorotoxin; treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Adhesion Molecules / chemistry
  • Cell Adhesion Molecules / genetics
  • Cell Adhesion Molecules / metabolism*
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Charybdotoxin / chemistry
  • Charybdotoxin / isolation & purification
  • Charybdotoxin / pharmacology
  • Chromatography, High Pressure Liquid
  • Disease Models, Animal
  • Estrogen Receptor alpha / chemistry
  • Estrogen Receptor alpha / genetics
  • Estrogen Receptor alpha / metabolism*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Mice
  • Microfilament Proteins / chemistry
  • Microfilament Proteins / genetics
  • Microfilament Proteins / metabolism*
  • Phosphoproteins / chemistry
  • Phosphoproteins / genetics
  • Phosphoproteins / metabolism*
  • Protein Binding
  • Scorpion Venoms / chemistry
  • Scorpion Venoms / isolation & purification
  • Scorpion Venoms / pharmacology*
  • Signal Transduction / drug effects*


  • Cell Adhesion Molecules
  • Estrogen Receptor alpha
  • Microfilament Proteins
  • Phosphoproteins
  • Scorpion Venoms
  • vasodilator-stimulated phosphoprotein
  • Chlorotoxin
  • Charybdotoxin