Unraveling the roles of fibroblast activation protein‑positive cancer‑associated fibroblasts in cancer: From mechanisms to therapy (Review)

Figures

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  Figure 1. Expression profile of FAP across human cancer. The bar indicates the percentage of patients (n=4-12) with high or medium FAP protein expression based on antibody staining. Data were obtained from the Human Protein Atlas (proteinatlas.org). FAP, fibroblast activation protein.

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  Figure 2. Marker- and function-defined CAF subsets. α-SMA+ CAFs (α-SMAhigh FAPlow CAFs) largely correspond to myCAFs. The majority of FAP+ CAFs exhibit iCAF-like functional states, whereas a minor proportion of double-positive subset (α-SMAhigh FAPhigh CAFs) display a myCAF-like phenotype. SMA, smooth muscle actin; myCAF, myofibroblastic cancer-associated fibroblast; FAP, fibroblast activation protein; i, inflammatory; ap, antigen-presenting.

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  Figure 3. Key roles of FAP+ CAFs in promoting tumor progression. FAP+ CAFs shape a pro-tumorigenic microenvironment by orchestrating ECM remodeling, fostering an immunosuppressive niche through immune cell recruitment and polarization, and mediating communication with tumor cells via direct contact, EVs and cytokine signaling. FAP, fibroblast activation protein; CAF, cancer-associated fibroblast; ECM, extracellular matrix; EV, extracellular vesicle; Treg, regulatory T cell; PDGF, platelet-derived growth factor.

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  Figure 4. FAP-mediated signaling networks in CAFs promoting tumor malignancy. CAF-derived FAP (including sFAP) promotes tumor cell EMT, proliferation and migration by activating downstream signaling pathways and inducing inflammatory cytokine secretion. sFAP, soluble fibroblast activation protein; CAF, cancer-associated fibroblasts; uPAR, urokinase-type plasminogen activator receptor; DNA-PKcs, DNA-dependent protein kinase catalytic subunit; ENO, enolase; FAK, focal adhesion kinase; EMT, epithelial-mesenchymal transition.