Department of Oncology, Georgetown Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, 3870 Reservoir Road NW, Washington, DC, 20057, USA.
Cancer Metastasis Rev. 2020 Sep;39(3):783-803. doi: 10.1007/s10555-020-09909-3.
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.
成纤维细胞激活蛋白-α（FAP）是一种 II 型跨膜丝氨酸蛋白酶，几乎只在包括纤维化、关节炎和癌症在内的病理条件下表达。在大多数癌症类型中，FAP 的升高与更差的临床结局相关。尽管 FAP 与疾病严重程度之间存在明确的关联，但这些临床观察背后的生物学原因尚不清楚。在这里，我们回顾了基础 FAP 生物学以及 FAP 在非肿瘤和肿瘤疾病中的作用。我们还进一步探讨了 FAP 如何通过对细胞外基质重塑、细胞内信号调节、血管生成、上皮-间充质转化和免疫抑制的影响来恶化临床结局。最后，我们讨论了利用 FAP 生物学来改善临床结局的潜力。
