ArticleProceedings of the National Academy of Sciences of the United States of America2001
Anti-apoptotic signaling by hepatocyte growth factor/Met via the phosphatidylinositol 3-kinase/Akt and mitogen-activated protein kinase pathways.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 152 papers.
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Who cites it
152 citing papers in PubMed, 395 citations in OpenAlex.
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- PPARβ/δ priming enhances mesenchymal stromal cell anti-apoptotic properties on chondrocytes via ANGPTL4 and improves their therapeutic effects in osteoarthritis.Stem cells translational medicine · 2026Article
- The transcription factor SREBP2 supports the activation and homeostasis of CD4+ Foxp3+ regulatory T cells.Journal of immunology (Baltimore, Md. : 1950) · 2026Article
- The HGF/MET Axis in Advanced Prostate Cancer: From Context-Dependent Biology to Biomarker-Driven Therapeutic Strategies.Cancers · 2026Review
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- Targeting MET and KRAS G12C co-occurring mutation in metastatic adenoid cystic carcinoma of the trachea: a case report.Journal of medical case reports · 2025Article
- SARS-CoV2 infection triggers inflammatory conditions and astrogliosis-related gene expression in long-term human cortical organoids.Stem cells (Dayton, Ohio) · 2025Article
- Targeting c-MET Alterations in Cancer: A Review of Genetic Drivers and Therapeutic Implications.Cancers · 2025Review
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- HGF/c-MET axis contributes to CLL cell survival by regulating multiple mechanisms making it a potential therapeutic target for CLL treatment.Frontiers in pharmacology · 2025Article
- Luteolin attenuates inflammation and apoptosis in LPS-induced ALI mice by activating the HGF/c-Met pathway.Frontiers in pharmacology · 2025Article
- CD44 variant exons induce chemoresistance by modulating cell death pathways.Frontiers in cell and developmental biology · 2025Review
- Evaluation of different media compositions promoting hepatocyte differentiation in the canine liver organoid model.Heliyon · 2024Article
- Targeting MET in NSCLC: An Ever-Expanding Territory.JTO clinical and research reports · 2024Review
- ATH-1105, a small-molecule positive modulator of the neurotrophic HGF system, is neuroprotective, preserves neuromotor function, and extends survival in preclinical models of ALS.Frontiers in neuroscience · 2024Article
- Inhibition of Cell Apoptosis by Apicomplexan Protozoa-Host Interaction in the Early Stage of Infection.Animals : an open access journal from MDPI · 2023Review
- Advances in stem cell therapy for peritoneal fibrosis: from mechanisms to therapeutics.Stem cell research & therapy · 2023Review
- The effect of hepatocyte growth factor on intestinal adaption in an experimental model of short bowel syndrome.Pediatric surgery international · 2023Article
- Article
92 more citing papers are in PubMed but not listed here.
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PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Hepatocyte growth factor (HGF) is a ligand of the receptor tyrosine kinase encoded by the c-Met protooncogene. HGF/Met signaling has multifunctional effects on various cell types. We sought to determine the role of HGF/Met in apoptosis and identify signal transducers involved in this process. In experiments with human SK-LMS-1 leiomyosarcoma cells, we show that the Akt kinase is activated by HGF in a time- and dose-dependent manner by phosphatidylinositol 3-kinase (PI3-kinase). Akt is also activated by active tumorigenic forms of Met, i.e., ligand-independent Tpr-Met, a truncated and constitutively dimerized form of Met, and a mutationally activated version of Met corresponding to that found in human hereditary papillary renal carcinoma. In NIH 3T3 cells transfected with wild-type Met, HGF inhibits apoptosis induced by serum starvation and UV irradiation. HGF-induced survival correlates with Akt activity and is inhibited by the specific PI3-kinase inhibitor LY294002, indicating that HGF inhibits cell death through the PI3-kinase/Akt signal transduction pathway. Furthermore, transiently transfected Tpr-Met activates Akt (both Akt1 and Akt2) and protects cells from apoptosis. Mitogen-activated protein kinase (MAPK) also is activated by HGF and rescues cells from apoptosis, although the cytoprotective effect is less marked than for PI3-kinase/Akt. Blocking MAPK with the specific MAPK kinase inhibitor PD098059 impairs the ability of HGF to promote cell survival. Similar results were obtained with NIH 3T3 cells expressing the fusion protein Trk-Met and stimulated with nerve growth factor, the Trk ligand. These results demonstrate that HGF/Met is capable of protecting cells from apoptosis by using both PI3-kinase/Akt and, to a lesser extent, MAPK pathways.
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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.