ArticleProceedings of the National Academy of Sciences of the United States of America2010
FGF receptor-4 (FGFR4) polymorphism acts as an activity switch of a membrane type 1 matrix metalloproteinase-FGFR4 complex.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
26 citing papers in PubMed, 52 citations in OpenAlex.
- FGFR4 in endocrine resistance: overexpression and estrogen regulation without direct causative role.Breast cancer research and treatment · 2025Article
- Drugging Hijacked Kinase Pathways in Pediatric Oncology: Opportunities and Current Scenario.Pharmaceutics · 2023Review
- Review
- Role of FGF15 in Hepatic Surgery in the Presence of Tumorigenesis: Dr. Jekyll or Mr. Hyde?Cells · 2021Review
- Src is essential for the endosomal delivery of the FGFR4 signaling complex in hepatocellular carcinoma.Journal of translational medicine · 2021Article
- FGFR4: A promising therapeutic target for breast cancer and other solid tumors.Pharmacology & therapeutics · 2020Review
- FGFR4 Gly388Arg Polymorphism Affects the Progression of Gastric Cancer by Activating STAT3 Pathway to Induce Epithelial to Mesenchymal Transition.Cancer research and treatment · 2020Article
- Crosstalk Between Cancer Associated Fibroblasts and Cancer Cells in Scirrhous Type Gastric Cancer.Frontiers in oncology · 2020Review
- FGFR4 phosphorylates MST1 to confer breast cancer cells resistance to MST1/2-dependent apoptosis.Cell death and differentiation · 2019Article
- The FGFR4-388arg Variant Promotes Lung Cancer Progression by N-Cadherin Induction.Scientific reports · 2018Article
- Functional FGFR4 Gly388Arg polymorphism contributes to oral squamous cell carcinoma susceptibility.Oncotarget · 2017Article
- The role ofActa medica Lituanic · 2017Article
- Roles of FGFR in oral carcinogenesis.Cell proliferation · 2016Review
- The Prognostic Significance of FGFR4 Gly388 Polymorphism in Esophageal Squamous Cell Carcinoma after Concurrent Chemoradiotherapy.Cancer research and treatment · 2016Article
- Membrane-Type 1 Matrix Metalloproteinase Downregulates Fibroblast Growth Factor-2 Binding to the Cell Surface and Intracellular Signaling.Journal of cellular physiology · 2015Article
- TIMP-2 Interaction with MT1-MMP Activates the AKT Pathway and Protects Tumor Cells from Apoptosis.PloS one · 2015Article
- Eph- and ephrin-dependent mechanisms in tumor and stem cell dynamics.Cellular and molecular life sciences : CMLS · 2014Review
- Actin-associated protein palladin promotes tumor cell invasion by linking extracellular matrix degradation to cell cytoskeleton.Molecular biology of the cell · 2014Article
- Is fibroblast growth factor receptor 4 a suitable target of cancer therapy?Current pharmaceutical design · 2014Review
- Functional roles of fibroblast growth factor receptors (FGFRs) signaling in human cancers.Apoptosis : an international journal on programmed cell death · 2013Review
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 3 countries.
Funding
Abstract
Tumor cells use membrane type 1 matrix metalloproteinase (MT1-MMP) for invasion and metastasis. However, the signaling mechanisms that underlie MT1-MMP regulation in cancer have remained unclear. Using a systematic gain-of-function kinome screen for MT1-MMP activity, we have here identified kinases that significantly enhance MT1-MMP activity in tumor cells. In particular, we discovered an MT1-MMP/FGF receptor-4 (FGFR4) membrane complex that either stimulates or suppresses MT1-MMP and FGFR4 activities, depending on a tumor progression-associated polymorphism in FGFR4. The FGFR4-R388 allele, linked to poor cancer prognosis, increased collagen invasion by decreasing lysosomal MT1-MMP degradation. FGFR4-R388 induced MT1-MMP phosphorylation and endosomal stabilization, and surprisingly, the increased MT1-MMP in return enhanced FGFR4-R388 autophosphorylation. A phosphorylation-defective MT1-MMP was stabilized on the cell surface, where it induced simultaneous FGFR4-R388 internalization and dissociation of cell-cell junctions. In contrast, the alternative FGFR4-G388 variant down-regulated MT1-MMP, and the overexpression of MT1-MMP and particularly its phosphorylation-defective mutant vice versa induced FGFR4-G388 degradation. These results provide a mechanistic basis for FGFR4-R388 function in cancer invasion.
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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 OpenQuestion graph.