ArticleClinical & experimental metastasis2015
Fibroblast activation protein increases metastatic potential of fibrosarcoma line HT1080 through upregulation of integrin-mediated signaling pathways.
Article in Clinical & experimental metastasis, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 28 citations in OpenAlex.
- Inhibition of fibroblast activation protein partially restores the homeostatic phenotype of mechanoactivated synoviocytes.Osteoarthritis and cartilage · 2026Article
- [Positron emission tomography in sarcomas].Radiologie (Heidelberg, Germany) · 2026Review
- The importance of mechanical forces in chronic respiratory diseases.European respiratory review : an official journal of the European Respiratory Society · 2026Review
- Evaluation of folate receptor-alpha and other surface markers as potential targets for radionuclide therapy of ovarian cancer.EJNMMI research · 2025Article
- A fibroblast activation protein targeted optical tracer for identifying primary and metastatic sarcoma during resection.EJNMMI research · 2025Article
- Targeting IDH1 mutation-driven Nrf2 signaling to suppress malignant behavior in fibrosarcoma cells.Toxicological research · 2025Article
- Review
- Evaluating [European journal of nuclear medicine and molecular imaging · 2024Article
- From basic research to clinical application: targeting fibroblast activation protein for cancer diagnosis and treatment.Cellular oncology (Dordrecht, Netherlands) · 2024Review
- The Prognostic and therapeutic value and clinical implications of fibroblast activation protein-α as a novel biomarker in colorectal cancer.Cell communication and signaling : CCS · 2023Review
- Establishment of FAP-overexpressing Cells for FAP-targeted Theranostics.Current medical science · 2023Article
- Review
- Molecular imaging of fibroblast activation protein after myocardial infarction using the novel radiotracer [Theranostics · 2021Article
- Imaging of Fibroblast Activation Protein Alpha Expression in a Preclinical Mouse Model of Glioma Using Positron Emission Tomography.Molecules (Basel, Switzerland) · 2020Article
- Amplification of a calcium channel subunit CACNG4 increases breast cancer metastasis.EBioMedicine · 2020Article
- Fibroblast Activation Protein-α Expressing Fibroblasts Promote Lymph Node Metastasis in Esophageal Squamous Cell Carcinoma.OncoTargets and therapy · 2020Article
- Review
- Pro-tumorigenic roles of fibroblast activation protein in cancer: back to the basics.Oncogene · 2018Review
- Fibroblast activation protein augments progression and metastasis of pancreatic ductal adenocarcinoma.JCI insight · 2017Article
- Expression of cancer-associated fibroblast-related proteins in thyroid papillary carcinoma.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The serine protease fibroblast activation protein (FAP) is selectively expressed on tumour-associated fibroblasts in most human epithelial tumours, as well as on some mesenchymal tumours such as sarcoma. High FAP expression is most often associated with poor outcome and increased metastasis. Here, we compare the in vitro metastatic potential of HT1080 fibrosarcoma cells with and without FAP expression in order to elucidate the mechanism by which FAP may influence metastasis. In the presence of FAP, cells were more adhesive to extracellular matrix proteins and migrated and invaded through Matrigel to a greater degree. The anti-FAP antibody ESC11, which caused internalization of FAP, decreased adhesion and migration, but only when cells expressed FAP. It was also found that blocking activity of integrins β1 and αvβ3 reduced both cell adhesion and migration and this effect was much more marked in FAP-expressing HT1080 cells than mock-transfected HT1080 cells. The expression or activation of intracellular proteins that form part of the downstream signaling of integrins, including integrin-linked kinase, Rac1 and focal adhesion kinase, was also upregulated when FAP was expressed, suggesting that FAP not only upregulates metastatic-like cell behaviours through interaction with integrins, but also influences the intracellular signaling of integrins. This was confirmed using both PI3 kinase and Src kinase inhibitors, which decreased adhesion and migration in FAP-expressing cells, but did not affect mock-transfected HT1080 cells. FAP is therefore a useful target for anti-cancer therapy, as not only is its expression tumour-selective, but its downregulation has the potential to reduce incidence of metastasis.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.