title: Wnt pathway activity in breast cancer sub-types and stem-like cells.
abstract: BACKGROUND
  Wnt signalling has been implicated in stem cell regulation however its role in breast cancer stem cell regulation remains unclear.
  
  
  METHODS
  We used a panel of normal and breast cancer cell lines to assess Wnt pathway gene and protein expression, and for the investigation of Wnt signalling within stem cell-enriched populations, mRNA and protein expression was analysed after the selection of anoikis-resistant cells. Finally, cell lines and patient-derived samples were used to investigate Wnt pathway effects on stem cell activity in vitro.
  
  
  RESULTS
  Wnt pathway signalling increased in cancer compared to normal breast and in both cell lines and patient samples, expression of Wnt pathway genes correlated with estrogen receptor (ER) expression. Furthermore, specific Wnt pathway genes were predictive for recurrence within subtypes of breast cancer. Canonical Wnt pathway genes were increased in breast cancer stem cell-enriched populations in comparison to normal breast stem cell-enriched populations. Furthermore in cell lines, the ligand Wnt3a increased whilst the inhibitor DKK1 reduced mammosphere formation with the greatest inhibitory effects observed in ER+ve breast cancer cell lines. In patient-derived metastatic breast cancer samples, only ER-ve mammospheres were responsive to the ligand Wnt3a. However, the inhibitor DKK1 efficiently inhibited both ER+ve and ER-ve breast cancer but not normal mammosphere formation, suggesting that the Wnt pathway is aberrantly activated in breast cancer mammospheres.
  
  
  CONCLUSIONS
  Collectively, these data highlight differential Wnt signalling in breast cancer subtypes and activity in patient-derived metastatic cancer stem-like cells indicating a potential for Wnt-targeted treatment in breast cancers.
authors.affiliation: Breakthrough Breast Cancer Research Unit, University of Manchester, Manchester, England. rlamb@picr.man.ac.uk
authors.forename: Rebecca
authors.initials: R
authors.lastname: Lamb
authors.forename: Matthew P
authors.initials: MP
authors.lastname: Ablett
authors.forename: Katherine
authors.initials: K
authors.lastname: Spence
authors.forename: Göran
authors.initials: G
authors.lastname: Landberg
authors.forename: Andrew H
authors.initials: AH
authors.lastname: Sims
authors.forename: Robert B
authors.initials: RB
authors.lastname: Clarke
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D018275:Carcinoma, Lobular / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D009362:Neoplasm Metastasis; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology; D009928:Organ Specificity; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D060509:Wnt3A Protein / Q000235:genetics* / Q000378:metabolism
chemical_list: C501126:DKK1 protein, human; D036341:Intercellular Signaling Peptides and Proteins; D011960:Receptors, Estrogen; C555510:WNT3A protein, human; D060509:Wnt3A Protein