ArticleMolecular oncology2016
Fibroblast activation protein-α, a stromal cell surface protease, shapes key features of cancer associated fibroblasts through proteome and degradome alterations.
Article in Molecular oncology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers, 3 of them syntheses that pooled it.
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Who cites it
68 citing papers in PubMed, 3 syntheses or guidelines pooled it, 105 citations in OpenAlex.
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- State-of-the-art of FAPI-PET imaging: a systematic review and meta-analysis.European journal of nuclear medicine and molecular imaging · 2021Pooled it
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- Oleuropein Ameliorates Bleomycin-Induced Pulmonary Fibrosis in Mice by Targeting TGF-β1 Signaling Pathway.Biomolecules · 2025Article
- Extracellular Matrix Signaling Cues: Biological Functions, Diseases, and Therapeutic Targets.MedComm · 2025Review
- Identification of functional and diverse circulating cancer-associated fibroblasts in metastatic castration-naïve prostate cancer patients.Molecular oncology · 2025Article
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- Based on small molecules: development and application of fibroblast activation protein inhibitors radiopharmaceutical in tumor precision therapy.Frontiers in pharmacology · 2025Review
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- Cervicovaginal lavages uncover growth factors as key biomarkers for early diagnosis and prognosis of endometrial cancer.Molecular biomedicine · 2024Article
- Head-to-head comparison of [Translational cancer research · 2024Article
- From basic research to clinical application: targeting fibroblast activation protein for cancer diagnosis and treatment.Cellular oncology (Dordrecht, Netherlands) · 2024Review
- Fibroblast activation protein: Pivoting cancer/chemotherapeutic insight towards heart failure.Biochemical pharmacology · 2024Review
- Comparison ofDiagnostics (Basel, Switzerland) · 2023Article
- Dendritic cells infected with recombinant adenoviral vector encoding mouse fibroblast activation protein-α and human livin α exert an antitumor effect against Lewis lung carcinoma in mice.Immunity, inflammation and disease · 2023Article
- Automated Synthesis of [Pharmaceuticals (Basel, Switzerland) · 2023Article
8 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 6 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cancer associated fibroblasts (CAFs) constitute an abundant stromal component of most solid tumors. Fibroblast activation protein (FAP) α is a cell surface protease that is expressed by CAFs. We corroborate this expression profile by immunohistochemical analysis of colorectal cancer specimens. To better understand the tumor-contextual role of FAPα, we investigate how FAPα shapes functional and proteomic features of CAFs using loss- and gain-of function cellular model systems. FAPα activity has a strong impact on the secreted CAF proteome ("secretome"), including reduced levels of anti-angiogenic factors, elevated levels of transforming growth factor (TGF) β, and an impact on matrix processing enzymes. Functionally, FAPα mildly induces sprout formation by human umbilical vein endothelial cells. Moreover, loss of FAPα leads to a more epithelial cellular phenotype and this effect was rescued by exogenous application of TGFβ. In collagen contraction assays, FAPα induced a more contractile cellular phenotype. To characterize the proteolytic profile of FAPα, we investigated its specificity with proteome-derived peptide libraries and corroborated its preference for cleavage carboxy-terminal to proline residues. By "terminal amine labeling of substrates" (TAILS) we explored FAPα-dependent cleavage events. Although FAPα acts predominantly as an amino-dipeptidase, putative FAPα cleavage sites in collagens are present throughout the entire protein length. In contrast, putative FAPα cleavage sites in non-collagenous proteins cluster at the amino-terminus. The degradomic study highlights cell-contextual proteolysis by FAPα with distinct positional profiles. Generally, our findings link FAPα to key aspects of CAF biology and attribute an important role in tumor-stroma interaction to FAPα.
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