The WNT-5a derived peptide, Foxy-5, possesses dual properties that impair progression of ERalpha negative breast cancer

Cell Cycle. 2009 Jun 15;8(12):1838-42. doi: 10.4161/cc.8863. Epub 2009 Jun 27.


Despite improvements in detection and treatment, breast cancer remains the most common female cancer worldwide, and metastatic associated mortality is a significant public health issue. Patients with tumors negative for estrogen receptor (ERalpha), have a particularly poor prognosis, partly due to their inability to respond to current endocrine treaments. Expression of Wnt-5a has been associated with prolonged recurrence free survivial in clinical material, and Wnt-5a also inhibits migration and invasion of breast cancer cell lines. Loss of Wnt-5a is associated with loss of ERalpha in clinical breast cancer material, and Wnt-5a signaling upregulates ERalpha in ERalpha negative breast cancer cell lines. A Wnt-5a derived hexapeptide, Foxy-5, has been developed and like Wnt-5a, increases adhesion and inhibits migration of breast cancer cells. Furthermore, Foxy-5 significantly reduced liver and lung metastases in a murine ERalpha negative breast cancer model. Foxy-5 also upregulated ERalpha in this in vivo model and most significantly, in vitro rendered cells responsive to the selective estrogen receptor modulator, Tamoxifen. Together these studies suggest that Foxy-5 may be a potential new supplementary treatment for ERalpha negative breast cancer patients, as it addresses two of the most important aspects of cancer related mortality -- non response to endocrine therapy and metastasis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review
  • Retracted Publication

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • Breast Neoplasms / classification
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / metabolism*
  • Estrogen Receptor alpha / metabolism
  • Female
  • Humans
  • Mice
  • Oligopeptides / metabolism*
  • Oligopeptides / pharmacology*
  • Oligopeptides / therapeutic use
  • Proto-Oncogene Proteins / metabolism*
  • Proto-Oncogene Proteins / pharmacology*
  • Proto-Oncogene Proteins / therapeutic use
  • Tamoxifen / pharmacology
  • Tamoxifen / therapeutic use
  • Wnt Proteins / metabolism*
  • Wnt Proteins / pharmacology*
  • Wnt Proteins / therapeutic use
  • Wnt-5a Protein


  • Antineoplastic Agents
  • Estrogen Receptor alpha
  • Foxy-5 peptide
  • Oligopeptides
  • Proto-Oncogene Proteins
  • WNT5A protein, human
  • Wnt Proteins
  • Wnt-5a Protein
  • Tamoxifen