ArticleGenes & cancer2015
MEK inhibition induces apoptosis in osteosarcoma cells with constitutive ERK1/2 phosphorylation.
Article in Genes & cancer, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 30 citations in OpenAlex.
- Chemoresistance-Related Stem Cell Signaling in Osteosarcoma and Its Plausible Contribution to Poor Therapeutic Response: A Discussion That Still Matters.International journal of molecular sciences · 2022Review
- A 3D-printed scaffold-based osteosarcoma model allows to investigate tumor phenotypes and pathogenesis in an in vitro bone-mimicking niche.Materials today. Bio · 2022Article
- Osteosarcoma tumor microenvironment: the key for the successful development of biologically relevant 3D in vitro models.In vitro models · 2022Review
- Pazopanib and Trametinib as a Synergistic Strategy against Osteosarcoma: Preclinical Activity and Molecular Insights.Cancers · 2020Article
- MicroRNA-mRNA networks define translatable molecular outcome phenotypes in osteosarcoma.Scientific reports · 2020Article
- Down-Regulation of Ribosomal Protein RPS21 Inhibits Invasive Behavior of Osteosarcoma Cells Through the Inactivation of MAPK Pathway.Cancer management and research · 2020Article
- What's new in bone forming tumours of the skeleton?Virchows Archiv : an international journal of pathology · 2020Review
- Linking drug target and pathway activation for effective therapy using multi-task learning.Scientific reports · 2018Article
- Relevance of 3d culture systems to study osteosarcoma environment.Journal of experimental & clinical cancer research : CR · 2018Review
- Article
- Clinical significance and prospective molecular mechanism of MALAT1 in pancreatic cancer exploration: a comprehensive study based on the GeneChip, GEO, Oncomine, and TCGA databases.OncoTargets and therapy · 2017Article
- Differences in MEK inhibitor efficacy in molecularly characterized low-grade serous ovarian cancer cell lines.American journal of cancer research · 2016Article
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Conventional high-grade osteosarcoma is the most common primary bone cancer with relatively high incidence in young people. Recurrent and metastatic tumors are difficult to treat. We performed a kinase inhibitor screen in two osteosarcoma cell lines, which identified MEK1/2 inhibitors. These inhibitors were further validated in a panel of six osteosarcoma cell lines. Western blot analysis was performed to assess ERK activity and efficacy of MEK inhibition. A 3D culture system was used to validate results from 2D monolayer cultures. Gene expression analysis was performed to identify differentially expressed gene signatures in sensitive and resistant cell lines. Activation of the AKT signaling network was explored using Western blot and pharmacological inhibition. In the screen, Trametinib, AZD8330 and TAK-733 decreased cell viability by more than 50%. Validation in six osteosarcoma cell lines identified three cell lines as resistant and three as sensitive to the inhibitors. Western blot analysis of ERK activity revealed that sensitive lines had high constitutive ERK activity. Treatment with the three MEK inhibitors in a 3D culture system validated efficacy in inhibition of osteosarcoma viability. MEK1/2 inhibition represents a candidate treatment strategy for osteosarcomas displaying high MEK activity as determined by ERK phosphorylation status.
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