The role of fibroblast activation protein in health and malignancy

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.

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Funding

This work was supported by grants from the NIH (R01 CA050633 (LMW), F30 CA239441 (AAF), and P30 CA051008 (LMW)). Figures were created with Biorender.com.

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Fitzgerald, A.A., Weiner, L.M. The role of fibroblast activation protein in health and malignancy. Cancer Metastasis Rev (2020). https://doi.org/10.1007/s10555-020-09909-3

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Keywords

  • Fibroblast activation protein (FAP)
  • Fibroblasts
  • Stroma
  • Invasion