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Review
. 2020 Sep;39(3):783-803.
doi: 10.1007/s10555-020-09909-3.

The role of fibroblast activation protein in health and malignancy

Allison A Fitzgerald  1 , Louis M Weiner  2
Affiliations
Review

The role of fibroblast activation protein in health and malignancy

Allison A Fitzgerald et al. Cancer Metastasis Rev. 2020 Sep.

Abstract

Fibroblast activation protein-α (FAP) is a type-II transmembrane serine protease expressed almost exclusively to pathological conditions including fibrosis, arthritis, and cancer. Across most cancer types, elevated FAP is associated with worse clinical outcomes. Despite the clear association between FAP and disease severity, the biological reasons underlying these clinical observations remain unclear. Here we review basic FAP biology and FAP's role in non-oncologic and oncologic disease. We further explore how FAP may worsen clinical outcomes via its effects on extracellular matrix remodeling, intracellular signaling regulation, angiogenesis, epithelial-to-mesenchymal transition, and immunosuppression. Lastly, we discuss the potential to exploit FAP biology to improve clinical outcomes.

Keywords: Fibroblast activation protein (FAP); Fibroblasts; Invasion; Stroma.

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Conflict of interest statement

Conflicts of Interest: All other authors declare no potential conflicts of interest to disclose.

Figures

Fig. 1.
Fig. 1.. Ribbon model of FAP structure
A schematic diagram of FAP domain structure (top) and ribbon models (bottom) depicting the FAP dimer. The seven-bladed β-propeller domain, αβ hydroxylase domain and β-propeller blade are highlighted. Figure created in biorender.com, PDB ID# 1Z68 [25].
Fig. 2.
Fig. 2.
Potential signaling pathways affected by FAP that are responsible for the tumor promoting phenotypes associated with FAP expression
See this image and copyright information in PMC

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