Promotion of cellular growth and motility is independent of enzymatic activity of fibroblast activation Protein-a.

Lv, B., Xie, F., Zhao, P., Ma, X., Jiang, Wen Guo ORCID: https://orcid.org/0000-0002-3283-1111, Yu, J., Zhang, X. and Jia, J. 2016. Promotion of cellular growth and motility is independent of enzymatic activity of fibroblast activation Protein-a. Cancer Genomics and Proteomics 13 (3) , pp. 201-208.

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Abstract

BACKGROUND: Fibroblast activation protein-alpha (FAPα) is a type-II integral membrane serine protease and is expressed in most stromal fibroblasts. Recent studies showed that FAPα is also expressed in certain cancer cells but its role is still uncertain. MATERIALS AND METHODS: We analyzed the non-enzymatic activity of FAPα in breast cancer cells by introducing an enzymatic mutant FAPα (FAPS624A), in which the serine catalytic triad was destroyed. FAPα overexpression and knockdown cells were generated as controls. RESULTS: Cellular growth and motility were markedly increased in MCF-7 cells overexpressing FAPα and enzymatic-mutant FAPS624A. This is consistent with observations in FAPα-silenced BT549 cells. Western blotting showed activation of phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT) and matrix metalloproteinase (MMP) 2/9 in both wild-type FAPα-overexpressing and enzymatic-mutant FAPS624A-overexpressing cells. CONCLUSION: Promotion of cellular growth and motility is independent of the enzymatic activity of FAPα in breast cancer cells. The PI3K/AKT and MMP2/9 signaling pathways might be involved in such regulation.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Subjects:	R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Uncontrolled Keywords:	Fibroblast activation protein-alpha; breast cancer; matrix metalloproteinase; phosphatidylinositol-3-kinase
Additional Information:	Open Access Article
Publisher:	International Institute of Anticancer Research
ISSN:	1109-6535
Funders:	Cancer Research Wales and Cardiff China Medical Scholarship
Date of First Compliant Deposit:	24 April 2016
Date of Acceptance:	23 December 2015
Last Modified:	04 May 2023 21:59
URI:	https://orca.cardiff.ac.uk/id/eprint/95082

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