ArticleAmerican journal of respiratory cell and molecular biology2008
HGF mediates cell proliferation of human mesothelioma cells through a PI3K/MEK5/Fra-1 pathway.
Article in American journal of respiratory cell and molecular biology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 69 citations in OpenAlex.
- Comprehensive map of the regulatory network triggered by MET exon 14 skipping reveals important involvement of the RAS-ERK signaling pathway.Cell death & disease · 2025Article
- FRA1 (Frontiers in cell and developmental biology · 2025Article
- Review
- The significance of ERK5 catalytic-independent functions in disease pathways.Frontiers in cell and developmental biology · 2023Review
- Extracellular Vesicles Isolated from Malignant Mesothelioma Cancer-Associated Fibroblasts Induce Pro-Oncogenic Changes in Healthy Mesothelial Cells.International journal of molecular sciences · 2022Article
- Medical and Surgical Care of Patients With Mesothelioma and Their Relatives Carrying Germline BAP1 Mutations.Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer · 2022Review
- Transglutaminase 2 enhances hepatocyte growth factor signaling to drive the mesothelioma cancer cell phenotype.Molecular carcinogenesis · 2022Article
- Review
- Asbestos-induced chronic inflammation in malignant pleural mesothelioma and related therapeutic approaches-a narrative review.Precision cancer medicine · 2021Article
- Molecular Mechanisms of Epithelial to Mesenchymal Transition Regulated by ERK5 Signaling.Biomolecules · 2021Review
- Asbestos induces mesothelial cell transformation via HMGB1-driven autophagy.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- The nuclear oncoprotein Fra-1: a transcription factor knocking on therapeutic applications' door.Oncogene · 2020Review
- How asbestos and other fibers cause mesothelioma.Translational lung cancer research · 2020Review
- SV40 and human mesothelioma.Translational lung cancer research · 2020Review
- Expression and function of FRA1 protein in tumors.Molecular biology reports · 2020Review
- Mesothelioma: Scientific clues for prevention, diagnosis, and therapy.CA: a cancer journal for clinicians · 2019Review
- Impact of ERK5 on the Hallmarks of Cancer.International journal of molecular sciences · 2019Review
- Bronchial extracellular matrix from COPD patients induces altered gene expression in repopulated primary human bronchial epithelial cells.Scientific reports · 2018Article
- Integrin-uPAR signaling leads to FRA-1 phosphorylation and enhanced breast cancer invasion.Breast cancer research : BCR · 2018Article
- Extracellular signal regulated kinase 5 and inflammasome in progression of mesothelioma.Oncotarget · 2018Article
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Authors and funding
8 authors at 5 institutions in 1 country.
Funding
Abstract
The ligand hepatocyte growth factor/scatter factor (HGF) and its receptor tyrosine kinase, c-Met, are highly expressed in most human malignant mesotheliomas (MMs) and may contribute to their increased growth and viability. Based upon our observation that RNA silencing of fos-related antigen 1 (Fra-1) inhibited c-met expression in rat mesotheliomas (1), we hypothesized that Fra-1 was a key player in HGF-induced proliferation in human MMs. In three of seven human MM lines evaluated, HGF increased Fra-1 levels and phosphorylation of both extracellular signal-regulated kinase 5 (ERK5) and AKT that were inhibited by the phosphatidylinositol 3-kinase (PI3K) inhibitor, LY290042. HGF-dependent phosphorylation and Fra-1 expression were decreased after knockdown of Fra-1, whereas overexpression of Fra-1 blocked the expression of mitogen/extracellular signal-regulated kinase kinases (MEK)5 at the mRNA and protein levels. Stable MM cell lines using a dnMEK5 showed that basal Fra-1 levels were increased in comparison to empty vector control lines. HGF also caused increased MM cell viability and proliferating cell nuclear antigen (PCNA) expression that were abolished by knockdown of MEK5 or Fra-1. Data suggest that HGF-induced effects in some MM cells are mediated via activation of a novel PI3K/ERK5/Fra-1 feedback pathway that might explain tumor-specific effects of c-Met inhibitors on MM and other tumors.
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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.