ArticleOncoTargets and therapy2021
A c-Met Inhibitor Suppresses Osteosarcoma Progression via the ERK1/2 Pathway in Human Osteosarcoma Cells.
Article in OncoTargets and therapy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 10 citations in OpenAlex.
- Different neutrophil extracellular trap related Ewing sarcoma subtypes exhibit distinct prognosis, and immune microenvironment characteristics.Scientific reports · 2025Article
- Cuproptosis related lncRNA signature as a prognostic and therapeutic biomarker in osteosarcoma immunity.Scientific reports · 2025Article
- The role and research progress of the MET signalling pathway in targeted therapy for osteosarcoma.Oncology reviews · 2025Review
- MAPK-targeted therapies in non-gastrointestinal stromal tumor soft tissue sarcomas: current landscape and future directions.Frontiers in oncology · 2025Review
- KLK8/HGF/Met signaling pathway mediates diabetes-associated hippocampal neuroinflammation in male mice.Theranostics · 2025Article
- Therapeutic potential of tyrosine-protein kinase MET in osteosarcoma.Frontiers in molecular biosciences · 2024Review
- Article
- Drugging Hijacked Kinase Pathways in Pediatric Oncology: Opportunities and Current Scenario.Pharmaceutics · 2023Review
- c-Met up-regulates the expression of PD-L1 through MAPK/NF-κBp65 pathway.Journal of molecular medicine (Berlin, Germany) · 2022Article
- Niclosamide Suppresses Migration and Invasion of Human Osteosarcoma Cells by Repressing TGFBI Expression via the ERK Signaling Pathway.International journal of molecular sciences · 2022Article
- Pathobiology and Molecular Pathways Implicated in Osteosarcoma Lung Metastasis: A Scoping Review.Technology in cancer research & treatmentArticle
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionOsteosarcoma is the most common primary malignancy of the bone among adolescents and children. Despite intensive chemotherapy and aggressive surgery, the 5-year survival rate of osteosarcoma still falls under 70%, mainly due to its tendency to metastasize and to develop drug resistance. Therefore, new treatments for osteosarcoma are urgently needed. HGF/c-Met signaling pathway, when dysregulated, is involved in the onset, progression and metastasis of various cancers, making the HGF/c-Met axis a promising therapeutic target.
methodsIn this study, we found Met to be a cancer-promoting gene in osteosarcoma as well, and aimed to investigate the role of a c-met inhibitor (PHA-665752) in osteosarcoma. For this purpose, two human osteosarcoma cell lines (143B and U2OS) were introduced in this study and treated with PHA-665752. CCK8 cell proliferation assay was performed to obtain the IC
resultsOur results showed that PHA-665752 could suppress osteosarcoma progression, promote apoptosis and inhibit proliferation of human osteosarcoma cells. Moreover, we found ERK1/2 pathway to be an important mediator underlying the osteosarcoma-suppressing function of PHA-665752. LY3214996, a highly selective inhibitor of the ERK1/2 pathway, was able to antagonize the effects of PHA-665752 in osteosarcoma. Finally, in vivo experiments indicated that PHA-665752 suppressed tumor growth in a tumor-transplanted mouse model.
conclusionTaken together, Met provided a druggable target for osteosarcoma and PHA-665752 is a promising candidate for anti-osteosarcoma treatments.
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