FAP-α (Fibroblast activation protein-α) is involved in the control of human breast cancer cell line growth and motility via the FAK pathway

Background: Fibroblast Activation Protein alpha (FAP-alpha) 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-alpha in human breast cancer. Expression of FAP-alpha was characterized in primary tumour samples and in cell lines, along with the effects of FAP-alpha expression on in vitro growth, invasion, attachment and migration. Furthermore the potential interaction of FAP-alpha with other signalling pathways was investigated. Results: FAP-alpha was significantly increased in patients with poor outcome and survival. In vitro results showed that breast cancer cells over expressing FAP-alpha 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-alpha expression. Over-expression of FAP-alpha 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, PLC gamma, NWASP, ARP2/3, and ROCK had no influence this. Conclusions: FAP-alpha in significantly associated with poor outcome in patients with breast cancer. In vitro, FAP-alpha promotes proliferation and inhibits migration of breast cancer cells, potentially by regulating the FAK pathway. These results suggest FAP-alpha could be a target for future therapies.