ArticleOncogene2011
Ligand-independent activation of c-Met by fibronectin and α(5)β(1)-integrin regulates ovarian cancer invasion and metastasis.
Article in Oncogene, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 175 papers, 1 of them a synthesis that pooled it.
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Who cites it
175 citing papers in PubMed, 1 synthesis or guideline pooled it, 259 citations in OpenAlex.
- Risk prediction for late-stage ovarian cancer by meta-analysis of 1525 patient samples.Journal of the National Cancer Institute · 2014Pooled it
- Clinical and biomarker results from a phase II trial of combined cabozantinib and durvalumab in patients with chemotherapy-refractory colorectal cancer (CRC): CAMILLA CRC cohort.Nature communications · 2024Trial
- C-MET tyrosine kinase receptor: mechanisms, clinical applications and future perspectives in cancer therapy.Signal transduction and targeted therapy · 2026Review
- GNAQ Induces Melanomagenesis in Mitfa-Independent Melanocyte Progenitors in a Zebrafish Model of Uveal Melanoma.Cancer research · 2026Article
- SPOCK1 acts as a negative regulator of ferroptosis in non-small cell lung cancer.NPJ precision oncology · 2026Article
- Met regulates endoderm migration in zebrafish.bioRxiv : the preprint server for biology · 2026Article
- Association of BRCA Mutation Status with Clinical Outcomes in High-Grade Serous Ovarian Cancer.Healthcare (Basel, Switzerland) · 2026Article
- A longitudinal, multi-omic atlas reveals the emergence of a spatially organized immunosuppressive ecosystem in resistant melanoma.Cell reports. Medicine · 2026Article
- ITGB1 Regulates Triple-Negative Breast Cancer Development by Modulating the Tumor Microenvironment.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Epitranscriptomic Regulation of Platinum Resistance via the METTL3-ADAM23 Axis in Ovarian Cancer.Cells · 2026Article
- Article
- Dynamic integrin expression, atypical nuclear localization, and spatial distribution during ovarian cancer progression and metastasis.Frontiers in cell and developmental biology · 2026Article
- Spatial proteomics of ovarian cancer precursors delineates early disease changes and drug targets.Molecular systems biology · 2026Article
- ITGA3-MET interaction promotes papillary thyroid cancer progression via ERK and PI3K/AKT pathways.Annals of medicine · 2025Article
- Alpha 5 integrin as a prognostic biomarker for survival in carcinomas: a systematic review.Discover oncology · 2025Review
- Article
- Interplay of integrins and selectins in metastasis.Molecular oncology · 2025Review
- Integrin-fibronectin interaction is a pivotal biological and clinical determinant in papillary thyroid carcinoma.Endocrine-related cancer · 2025Article
- Targeting c-MET Alterations in Cancer: A Review of Genetic Drivers and Therapeutic Implications.Cancers · 2025Review
- Extracellular vesicles in cancer´s communication: messages we can read and how to answer.Molecular cancer · 2025Review
115 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
The role of the fibronectin receptor, α(5)β(1)-integrin, as an adhesion receptor and in angiogenesis is well established. However, its role in cancer cell invasion and metastasis is less clear. We describe a novel mechanism by which fibronectin regulates ovarian cancer cell signaling and promotes metastasis. Fibronectin binding to α(5)β(1)-integrin led to a direct association of α(5)-integrin with the receptor tyrosine kinase, c-Met, activating it in a hepatocyte growth factor/scatter factor (HGF/SF) independent manner. Subsequently, c-Met associated with Src, and activated Src and focal adhesion kinase (FAK). Inhibition of α(5)β(1)-integrin decreased the phosphorylation of c-Met, FAK and Src, both in vitro and in vivo. Independent activation of c-Met by its native ligand, HGF/SF, or overexpression of a constitutively active FAK in HeyA8 cells could overcome the effect of α(5)β(1)-integrin inhibition on tumor cell invasion, indicating that α(5)β(1)-integrin is upstream of c-Met, Src and FAK. Inhibition of α(5)β(1)-integrin on cancer cells in two xenograft models of ovarian cancer metastasis resulted in a significant decrease of tumor burden, which was independent of the effect of α(5)β(1)-integrin on angiogenesis. These data suggest that fibronectin promotes ovarian cancer invasion and metastasis through an α(5)β(1)-integrin/c-Met/FAK/Src-dependent signaling pathway, transducing signals through c-Met in an HGF/SF-independent manner.
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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.