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

Jia, Jun, Martin, Tracey Amanda ORCID: https://orcid.org/0000-0003-2690-4908, Ye, Lin ORCID: https://orcid.org/0000-0002-0303-2409 and Jiang, Wen Guo ORCID: https://orcid.org/0000-0002-3283-1111 2014. FAP-alpha (Fibroblast activation protein-alpha) is involved in the control of human breast cancer cell line growth and motility via the FAK pathway. BMC Cell Biology 15 , 16. 10.1186/1471-2121-15-16

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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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Subjects:	R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Uncontrolled Keywords:	FAP-α; FAK; Breast Cancer; Growth; Migration
Additional Information:	© 2014 Jia et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited.
Publisher:	BioMed Central
ISSN:	1471-2121
Date of First Compliant Deposit:	30 March 2016
Date of Acceptance:	15 May 2014
Last Modified:	08 May 2023 19:52
URI:	https://orca.cardiff.ac.uk/id/eprint/75794

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