title: The WNT-5a derived peptide, Foxy-5, possesses dual properties that impair progression of ERalpha negative breast cancer.
abstract: 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.
authors.affiliation: Cell and Experimental Pathology, Department of Laboratory Medicine, Lund University, Malmö University Hospital, Malmö, Sweden. caroline.ford@med.lu.se
authors.forename: Caroline E
authors.initials: CE
authors.lastname: Ford
authors.forename: Elin J
authors.initials: EJ
authors.lastname: Ekström
authors.forename: Jillian
authors.initials: J
authors.lastname: Howlin
authors.forename: Tommy
authors.initials: T
authors.lastname: Andersson
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000145:classification / Q000188:drug therapy* / Q000378:metabolism*; D047628:Estrogen Receptor alpha / Q000378:metabolism; D005260:Female; D006801:Humans; D051379:Mice; D009842:Oligopeptides / Q000378:metabolism* / Q000494:pharmacology* / Q000627:therapeutic use; D011518:Proto-Oncogene Proteins / Q000378:metabolism* / Q000494:pharmacology* / Q000627:therapeutic use; D013629:Tamoxifen / Q000494:pharmacology / Q000627:therapeutic use; D051153:Wnt Proteins / Q000378:metabolism* / Q000494:pharmacology* / Q000627:therapeutic use; D000071818:Wnt-5a Protein
chemical_list: D000970:Antineoplastic Agents; D047628:Estrogen Receptor alpha; C542624:Foxy-5 peptide; D009842:Oligopeptides; D011518:Proto-Oncogene Proteins; C085389:WNT5A protein, human; D051153:Wnt Proteins; D000071818:Wnt-5a Protein; D013629:Tamoxifen