title: FAP-α (Fibroblast activation protein-α) is involved in the control of human breast cancer cell line growth and motility via the FAK pathway.
abstract: BACKGROUND
  Fibroblast Activation Protein alpha (FAP-α) or seprase is an integral membrane serine peptidase. Previous work has not satisfactorily explained both the suppression and promotion effects that have been observed in cancer. The purpose of this work was to investigate the role of FAP-α in human breast cancer. Expression of FAP-α was characterized in primary tumour samples and in cell lines, along with the effects of FAP-α expression on in vitro growth, invasion, attachment and migration. Furthermore the potential interaction of FAP-α with other signalling pathways was investigated.
  
  
  RESULTS
  FAP-α was significantly increased in patients with poor outcome and survival. In vitro results showed that breast cancer cells over expressing FAP-α had increased growth ability and impaired migratory ability. The growth of MDA-MB-231 cells and the adhesion and invasion ability of both MCF-7 cells and MDA-MB-231 cells were not dramatically influenced by FAP-α expression. Over-expression of FAP-α resulted in a reduction of phosphorylated focal adhesion kinase (FAK) level in both cells cultured in normal media and serum-free media. An inhibitor to FAK restored the reduced motility ability of both MCF-7exp cells and MDA-MB-231exp cells and prevented the change in phosphorylated FAK levels. However, inhibitors to PI3K, ERK, PLCΥ, NWASP, ARP2/3, and ROCK had no influence this.
  
  
  CONCLUSIONS
  FAP-α in significantly associated with poor outcome in patients with breast cancer. In vitro, FAP-α promotes proliferation and inhibits migration of breast cancer cells, potentially by regulating the FAK pathway. These results suggest FAP-α could be a target for future therapies.
authors.affiliation: Cardiff University-Peking University Cancer Institute, Cardiff University School of Medicine, Cardiff CF14 4XNWales, UK. vm26jun@gmail.com.
authors.forename: Jun
authors.initials: J
authors.lastname: Jia
authors.forename: Tracey Amanda
authors.initials: TA
authors.lastname: Martin
authors.forename: Lin
authors.initials: L
authors.lastname: Ye
authors.forename: Wen Guo
authors.initials: WG
authors.lastname: Jiang
mesh_terms: D001940:Breast / Q000378:metabolism / Q000473:pathology; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D010450:Endopeptidases; D005260:Female; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism*; D018093:Gelatinases / Q000378:metabolism*; D006801:Humans; D061986:MCF-7 Cells; D008565:Membrane Proteins / Q000378:metabolism*; D010766:Phosphorylation; D012697:Serine Endopeptidases / Q000378:metabolism*; D015398:Signal Transduction; D000099167:Fibroblast Activation Protein Alpha
chemical_list: D010450:Endopeptidases; D051416:Focal Adhesion Protein-Tyrosine Kinases; D018093:Gelatinases; D008565:Membrane Proteins; D012697:Serine Endopeptidases; D000099167:Fibroblast Activation Protein Alpha