title: Targeting focal adhesion turnover in invasive breast cancer cells by the purine derivative reversine.
abstract: BACKGROUND
  The dynamics of focal adhesion (FA) turnover is a key determinant for the regulation of cancer cell migration. Here we investigated FA turnover in a panel of breast cancer models with distinct invasive properties and evaluated the impact of reversine on this turnover in relation to cancer cell invasion in in vitro and in vivo conditions.
  
  
  METHODS
  Live imaging and immunofluorescence assays were used to investigate FA turnover in breast cancer cells. Biochemical studies were used to investigate the impact of reversine on FA signalling and turnover. In vivo activity was investigated using orthotopic breast cancer mouse models.
  
  
  RESULTS
  Accelerated FA disassembly from plasma membrane protrusions was observed in invasive compared with non-invasive breast cancer cells or non-immortalised mammary epithelial cells. Reversine significantly inhibited FA disassembly leading to stable FAs, which was associated with reduced cell motility and invasion. The inhibitory effect of reversine on FA turnover accounted for a large part on its capacity to interfere with FAK function on regulating its downstream targets. In orthotopic breast cancer mouse models, reversine revealed a potent inhibitory activity on tumour progression to metastasis.
  
  
  CONCLUSIONS
  These results support the utility of targeting FA turnover as a therapeutic approach for invasive breast cancer.
authors.affiliation: Departments of Medicine and Oncology, Segal Cancer Centre and Lady Davis Institute of the Sir Mortimer B. Davis Jewish General Hospital, McGill University, Montreal, Quebec H3T 1E2, Canada.
authors.forename: K
authors.initials: K
authors.lastname: Bijian
authors.forename: C
authors.initials: C
authors.lastname: Lougheed
authors.forename: J
authors.initials: J
authors.lastname: Su
authors.forename: B
authors.initials: B
authors.lastname: Xu
authors.forename: H
authors.initials: H
authors.lastname: Yu
authors.forename: J H
authors.initials: JH
authors.lastname: Wu
authors.forename: K
authors.initials: K
authors.lastname: Riccio
authors.forename: M A
authors.initials: MA
authors.lastname: Alaoui-Jamali
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000188:drug therapy* / Q000473:pathology; D002478:Cells, Cultured; D005260:Female; D022001:Focal Adhesions / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D061986:MCF-7 Cells; D051379:Mice; D016513:Mice, SCID; D058990:Molecular Targeted Therapy; D009025:Morpholines / Q000627:therapeutic use*; D011687:Purines / Q000627:therapeutic use*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D009025:Morpholines; D011687:Purines; C484369:2-(4-morpholinoanilino)-6-cyclohexylaminopurine