Related Experiment Video
Updated: May 23, 2026
Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells
Published on: October 27, 2020
Signal transduction pathway analysis in fibromatosis: receptor and nonreceptor tyrosine kinases
Justin M M Cates1, Jennifer O Black, Doha M Itani
1Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA. justin.m.cates@vanderbilt.edu
Abstract:
Despite reports of receptor tyrosine kinase activation in desmoid-type fibromatosis, therapeutic benefits of kinase inhibitor therapy are unpredictable. Variability in signal transduction or cellular kinases heretofore unevaluated in desmoid tumors may be responsible for these inconsistent responses. In either case, a better understanding of growth regulatory signaling pathways is necessary to assess the theoretical potential of inhibitor therapy. Immunohistochemical analysis of tyrosine kinases and activated isoforms of downstream signal transduction proteins was performed on a tissue microarray containing 27 cases of desmoid-type fibromatosis and 14 samples of scar; 6 whole sections of normal fibrous tissue were studied for comparison. Platelet-derived growth factor receptor, β type, and focal adhesion kinase 1 were expressed in all desmoid tumors and healing scars but only 80% and 50% of nonproliferative fibrous tissue samples, respectively. Hepatocyte growth factor receptor was detected in 89% of desmoids and all scars tested, but not in any of the fibrous tissue samples. Epidermal growth factor receptor was detected in only 12% of desmoids and not in scar or fibrous tissue. Mast/stem cell growth factor receptor, receptor tyrosine-protein kinase erbB-2, and phosphorylated insulin-like growth factor 1 receptor/insulin receptor were negative in all study cases. Variable levels of phosphorylated downstream signal transduction molecules RAC-α/β/γ serine/threonine-protein kinase, mitogen-activated protein kinase, and signal transducer and activator of transcription-3 were observed in desmoids (58%, 62%, and 67%), scar tissues (100%, 86%, and 86%), and fibrous tissue (33%, 17%, and 17%). These results indicate that tyrosine kinase signaling is active in both fibromatosis and healing scar, but not in most nonproliferating fibrous tissues. Although platelet-derived growth factor receptor, β type, is expressed ubiquitously in desmoids, the kinases driving cell proliferation in desmoids remain unresolved.
Insights
Understanding tyrosine kinase signaling in desmoid tumors is crucial for predicting kinase inhibitor therapy response. This study reveals active signaling in desmoids and scars, but the specific kinases driving desmoid proliferation remain unclear.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Receptor tyrosine kinase (RTK) activation is reported in desmoid-type fibromatosis, but kinase inhibitor therapy outcomes are inconsistent.
- Variability in signal transduction pathways or unstudied kinases may explain unpredictable therapeutic responses.
- A deeper understanding of growth regulatory signaling in desmoid tumors is needed to evaluate targeted therapies.
Purpose of the Study:
- To investigate the expression and activation status of various tyrosine kinases and downstream signaling proteins in desmoid-type fibromatosis.
- To compare signaling pathways in desmoid tumors with those in healing scars and normal fibrous tissue.
- To identify potential therapeutic targets for desmoid-type fibromatosis.
Main Methods:
- Immunohistochemical analysis was performed on a tissue microarray of 27 desmoid tumors, 14 scars, and 6 normal fibrous tissue samples.
- Expression of specific tyrosine kinases (PDGFR-β, FGFR, EGFR, c-KIT, HER2) and downstream signaling molecules (FAK, p-MAPK, p-STAT3, p-AKT) was assessed.
- Comparison of protein expression patterns between desmoid tumors, scars, and normal fibrous tissue.
Main Results:
- Platelet-derived growth factor receptor, β type (PDGFR-β) and focal adhesion kinase 1 (FAK1) were expressed in all desmoids and scars.
- Hepatocyte growth factor receptor (HGFR) was detected in most desmoids (89%) and all scars.
- Variable activation of RAC-α/β/γ serine/threonine-protein kinase (Akt), mitogen-activated protein kinase (MAPK), and signal transducer and activator of transcription-3 (STAT3) was observed in desmoids and scars, but not in normal fibrous tissue.
Conclusions:
- Tyrosine kinase signaling is active in both desmoid-type fibromatosis and healing scars, distinguishing them from non-proliferative fibrous tissue.
- While PDGFR-β is ubiquitously expressed in desmoids, the specific kinases driving desmoid cell proliferation remain unidentified.
- Further research is needed to elucidate the precise signaling pathways involved in desmoid tumor growth and to optimize kinase inhibitor therapy.
More Related Videos
Related Concept Videos
01:26Receptor Tyrosine Kinases
01:27Transducer Mechanism: Enzyme-Linked Receptors
Major types that are helpful drug targets include:
01:16TGF - β Signaling Pathway
01:22Amplifying Signals via Enzymatic Cascade
01:00Enzyme-linked Receptors
Neurotrophin (NT) receptors are a family of RTKs, including trkA, trkB, and trkC (tropomyosin-related kinase) receptors. TrkA is specific for nerve growth factor (NGF), neurotrophin-6, and neurotrophin-7. TrkB binds...
01:19Interactions Between Signaling Pathways
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...