ArticlePloS one2011
Polarized endocytosis of the keratinocyte growth factor receptor in migrating cells: role of SRC-signaling and cortactin.
Article in PloS one, 2011. 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, 30 citations in OpenAlex.
- Receptor tyrosine kinase signaling in mammalian eye development.Developmental biology · 2026Review
- Wnt signaling pathways in biology and disease: mechanisms and therapeutic advances.Signal transduction and targeted therapy · 2025Review
- FGF receptor kinase inhibitors exhibit broad antiviral activity by targeting Src family kinases.Cellular and molecular life sciences : CMLS · 2024Article
- Interaction of human keratinocytes and nerve fiber terminals at the neuro-cutaneous unit.eLife · 2024Article
- A seven-autophagy-related gene signature for predicting the prognosis of differentiated thyroid carcinoma.World journal of surgical oncology · 2022Article
- Epidermal Growth Factor Receptor's Function in Cutaneous Squamous Cell Carcinoma and Its Role as a Therapeutic Target in the Age of Immunotherapies.Current treatment options in oncology · 2020Review
- Inhibition of non-receptor tyrosine kinase Src induces phosphoserine 256-independent aquaporin-2 membrane accumulation.The Journal of physiology · 2019Article
- Regulation and Role of GLI1 in Cutaneous Squamous Cell Carcinoma Pathogenesis.Frontiers in genetics · 2019Article
- Genome-wide transcriptome analysis identifies alternative splicing regulatory network and key splicing factors in mouse and human psoriasis.Scientific reports · 2018Article
- Temperature-sensitive heparin-modified poloxamer hydrogel with affinity to KGF facilitate the morphologic and functional recovery of the injured rat uterus.Drug delivery · 2017Article
- BRCA1-IRIS overexpression promotes and maintains the tumor initiating phenotype: implications for triple negative breast cancer early lesions.Oncotarget · 2017Article
- Keratinocyte Growth Factor Combined with a Sodium Hyaluronate Gel Inhibits Postoperative Intra-Abdominal Adhesions.International journal of molecular sciences · 2016Article
- FAK, talin and PIPKIγ regulate endocytosed integrin activation to polarize focal adhesion assembly.Nature cell biology · 2016Article
- Expression of the FGFR2 mesenchymal splicing variant in epithelial cells drives epithelial-mesenchymal transition.Oncotarget · 2016Article
- In vivo over-expression of KGF mimic human middle ear cholesteatoma.European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery · 2015Article
- On the move: endocytic trafficking in cell migration.Cellular and molecular life sciences : CMLS · 2015Review
- Polarised clathrin-mediated endocytosis of EGFR during chemotactic invasion.Traffic (Copenhagen, Denmark) · 2014Article
- FGF7/KGF regulates autophagy in keratinocytes: A novel dual role in the induction of both assembly and turnover of autophagosomes.Autophagy · 2014Article
- Effects of membrane trafficking on signaling by receptor tyrosine kinases.Cold Spring Harbor perspectives in biology · 2013Review
- Stathmin regulates keratinocyte proliferation and migration during cutaneous regeneration.PloS one · 2013Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cell migration is a physiological process that requires endocytic trafficking and polarization of adhesion molecules and receptor tyrosine kinases (RTKs) to the leading edge. Many growth factors are able to induce motility by binding to specific RTK on target cells. Among them, keratinocyte growth factor (KGF or FGF7) and fibroblast growth factor 10 (FGF10), members of the FGF family, are motogenic for keratinocytes, and exert their action by binding to the keratinocyte growth factor receptor (KGFR), a splicing variant of FGFR2, exclusively expressed on epithelial cells. Here we analyzed the possible role of cortactin, an F-actin binding protein which is tyrosine phosphorylated by Src and is involved in KGFR-mediated cell migration, in the KGFR endocytosis and polarization to the leading edge of migrating cells upon ligand-induced stimulation. Biochemical phosphorylation study revealed that both KGF and FGF10 were able to induce tyrosine phosphorylation of Src and in turn of cortactin, as demonstrated by using the specific pharmacological Src-inhibitor SU6656, although FGF10 effect was delayed with respect to that promoted by KGF. Immunofluorescence analysis demonstrated the polarized localization of KGFR upon ligand stimulation to the leading edge of migrating keratinocytes, process that was regulated by Src. Moreover, we showed that the colocalization of cortactin with KGFR at the plasma membrane protrusions and on early endosomes after KGF and FGF10 treatment was Src-dependent. Further, by using a RNA interference approach through microinjection, we showed that cortactin is required for KGFR endocytosis and that the clathrin-dependent internalization of the receptor is a critical event for its polarization. Finally, KGFR expression and polarization enhanced cell migration in a scratch assay. Our results indicate that both Src and cortactin play a key role in the KGFR endocytosis and polarization at the leading edge of migrating keratinocytes, supporting the crucial involvement of RTK trafficking in cell motility.
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