Identifiers
fibroblast activation protein alpha
HUGO:FAP hgnc_id:HGNC:3590 HGNC:3590 ENTREZ:2191 UNIPROT:Q12884
Maps_Modules
HMC:TUMOR_PROMOTING_INFLAMMATION
HMC:ACTIVATING_INVASION_AND_METASTASIS
Cancer Associated Fibroblasts / INFLAMMATORY_SIGNALING_PATHWAYS
Cancer Associated Fibroblasts / FIBROBLAST_ACTIVATION_MARKERS
References
CASCADE:HGF
CASCADE:TGFB
CASCADE:PLAU
PMID:25593080
Fibroblast activation protein ?? in tumor microenvironment: Recent progression and implications (Review)
FAP?? expression may be elevated under the influence of an altered tumor microenvironment or inflammation. In vitro FAP?? expression was observed in fibroblasts and melanocytes cultured in fibroblast growth factor (FGF) and phorbol ester (33). Treatment of FB20 cells with human transforming growth factor-??l (TGF-??1), 12-o-tetradecanoyl phorbol-13-acetate (TPA), retinol or retinoic acid for 24???48 h increased FAP?? expression in the cells (34). FAP?? expression in CD strictured myofibroblasts under the stimulation of 10 ng/ml tumor necrosis factor ?? (TNF-??) or TGF-??1 for 48 h was significantly increased (59). TNF-??, produced by macrophages, was also able to induce FAP?? expression in cultured human aortic smooth muscle cells (60). Further to the cytokines and chemical substances which induce FAP?? expression, physical stimulants, including ultraviolet radiation, also induce upregulation of FAP?? expression in fibroblasts, melanocytes and primary melanoma cells to facilitate invasion and migration of the cells (69).
FAP?? is a tumor promoter.
Silencing FAP?? with short interfering RNA transfected using a lentiviral vector inhibited growth and resulted in cell cycle arrest at the G2 and S phases of cancer-associated fibroblasts in vitro (73).
FAP?? displays DPP and gelatinolytic activity as proved by gelatin zymography and can cleave native ECM proteins, including collagen I, collagen IV, fibronectin, laminin and gelatin (38???40,49,86). These enzyme activities depend on the mutation at position Ser624, which abrogates the DPP and collagenase activity of FAP?? (49). These enzymatic activities indicate that FAP?? may have a prominent role in tumor invasion, metastasis and angiogenesis (86???88). Clinical observation revealed that the overexpression of FAP?? by ductal carcinomas is congruent with the invasion and metastasis of infiltrating ductal carcinomas (IDC) of the breast (55). Using an in vivo-like three-dimensional matrix system, Lee et al (89) observed that FAP?? remodeled the ECM and increased the invasive capability and metastasis of pancreatic tumors, mediated by ??1-integrin/focal adhesion kinase.
PMID:7911242
FAP is originally identified as a membrane-bound serine protease implicated in extracellular matrix remodeling
PMID:27216177
PlAUR induces FAK activation downstream of FAP, which directly interacts with PLAUR.
PMID:23402812
Hepatocyte growth factor activates tumor stromal fibroblasts to promote tumorigenesis in gastric cancer.
HGF induces expression markers of activated fibroblasts such as FAP, CXCL12 (SDF1),aplpha-SMA
PMID:24778314
Review about FAP
PMID:21051638
FAP-expressing cells are a nonredundant, immune-suppressive component of the tumor microenvironment.