ArticleThe Journal of biological chemistry2014
Role of c-Met/phosphatidylinositol 3-kinase (PI3k)/Akt signaling in hepatocyte growth factor (HGF)-mediated lamellipodia formation, reactive oxygen species (ROS) generation, and motility of lung endothelial cells.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.
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Who cites it
61 citing papers in PubMed, 89 citations in OpenAlex.
- Exposure-response analyses for the MET inhibitor tepotinib including patients in the pivotal VISION trial: support for dosage recommendations.Cancer chemotherapy and pharmacology · 2022Trial
- FARP1 mediates cMET-driven motility in androgen-independent prostate cancer cells.Endocrinology · 2026Article
- C-MYC as a key effector of WNT, PI3K/AKT, MAPK, and TGF-β signaling pathways in regulation of epithelial-mesenchymal transition during tumor metastasis.Cancer cell international · 2026Review
- ARID1A loss enhances sensitivity to c-MET inhibition by dual targeting of GPX4 and iron homeostasis, inducing ferroptosis.Cell death and differentiation · 2025Article
- Article
- Targeting c-MET Alterations in Cancer: A Review of Genetic Drivers and Therapeutic Implications.Cancers · 2025Review
- Advancements in Protein Kinase Inhibitors: From Discovery to Clinical Applications.Research (Washington, D.C.) · 2025Review
- Explainable machine learning prediction of edema adverse events in patients treated with tepotinib.Clinical and translational science · 2024Article
- Review
- Fabricating Composite Cell Sheets for Wound Healing: Cell Sheets Based on the Communication Between BMSCs and HFSCs Facilitate Full-Thickness Cutaneous Wound Healing.Tissue engineering and regenerative medicine · 2024Article
- Cross-talk between gastric cancer and hepatic stellate cells promotes invadopodia formation during liver metastasis.Cancer science · 2024Article
- In Silico Evaluation of HN-N07 Small Molecule as an Inhibitor of Angiogenesis and Lymphangiogenesis Oncogenic Signatures in Non-Small Cell Lung Cancer.Biomedicines · 2023Article
- Ran GTPase and Its Importance in Cellular Signaling and Malignant Phenotype.International journal of molecular sciences · 2023Review
- A combination of metformin and epigallocatechin gallate potentiates glioma chemotherapyFrontiers in pharmacology · 2023Article
- Effect of miR-21-3p on lung injury in rats with traumatic hemorrhagic shock resuscitated with sodium bicarbonate Ringer's solution.Annals of translational medicine · 2022Article
- Article
- Anti-cancer therapeutic strategies based on HGF/MET, EpCAM, and tumor-stromal cross talk.Cancer cell international · 2022Review
- IFITM3 promotes malignant progression, cancer stemness and chemoresistance of gastric cancer by targeting MET/AKT/FOXO3/c-MYC axis.Cell & bioscience · 2022Article
- Artonin F Induces the Ubiquitin-Proteasomal Degradation of c-Met and Decreases Akt-mTOR Signaling.Pharmaceuticals (Basel, Switzerland) · 2022Article
- Cortactin in Lung Cell Function and Disease.International journal of molecular sciences · 2022Review
1 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
Hepatocyte growth factor (HGF) mediated signaling promotes cell proliferation and migration in a variety of cell types and plays a key role in tumorigenesis. As cell migration is important to angiogenesis, we characterized HGF-mediated effects on the formation of lamellipodia, a pre-requisite for migration using human lung microvascular endothelial cells (HLMVECs). HGF, in a dose-dependent manner, induced c-Met phosphorylation (Tyr-1234/1235, Tyr-1349, Ser-985, Tyr-1003, and Tyr-1313), activation of PI3k (phospho-Yp85) and Akt (phospho-Thr-308 and phospho-Ser-473) and potentiated lamellipodia formation and HLMVEC migration. Inhibition of c-Met kinase by SU11274 significantly attenuated c-Met, PI3k, and Akt phosphorylation, suppressed lamellipodia formation and endothelial cell migration. LY294002, an inhibitor of PI3k, abolished HGF-induced PI3k (Tyr-458), and Akt (Thr-308 and Ser-473) phosphorylation and suppressed lamellipodia formation. Furthermore, HGF stimulated p47(phox)/Cortactin/Rac1 translocation to lamellipodia and ROS generation. Moreover, inhibition of c-Met/PI3k/Akt signaling axis and NADPH oxidase attenuated HGF- induced lamellipodia formation, ROS generation and cell migration. Ex vivo experiments with mouse aortic rings revealed a role for c-Met signaling in HGF-induced sprouting and lamellipodia formation. Taken together, these data provide evidence in support of a significant role for HGF-induced c-Met/PI3k/Akt signaling and NADPH oxidase activation in lamellipodia formation and motility of lung endothelial cells.
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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.