ArticlePloS one2013
FHL2 silencing reduces Wnt signaling and osteosarcoma tumorigenesis in vitro and in vivo.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 45 citations in OpenAlex.
- Comprehensive analysis of the prognostic and immunological role of cavins in non-small cell lung cancer.BMC cancer · 2024Article
- The roles of FHL2 as a mechanotransducer for cellular functions in the mechanical environment.Frontiers in cell and developmental biology · 2024Review
- HBXIP knockdown inhibits FHL2 to promote cycle arrest and suppress cervical cancer cell proliferation, invasion and migration.Oncology letters · 2023Article
- The role of WNT10B in physiology and disease: A 10-year update.Frontiers in cell and developmental biology · 2023Review
- Article
- Integrated DNA Copy Number and Expression Profiling Identifies IGF1R as a Prognostic Biomarker in Pediatric Osteosarcoma.International journal of molecular sciences · 2022Article
- High level of FHL2 exacerbates the outcome of non-small cell lung cancer (NSCLC) patients and the malignant phenotype in NSCLC cells.International journal of experimental pathology · 2022Article
- Article
- The titin N2B and N2A regions: biomechanical and metabolic signaling hubs in cross-striated muscles.Biophysical reviews · 2021Review
- FHL3 Contributes to EMT and Chemotherapy Resistance Through Up-Regulation of Slug and Activation of TGFFrontiers in oncology · 2021Article
- Osteosarcoma and Metastasis.Frontiers in oncology · 2021Review
- Association of the Epithelial-Mesenchymal Transition (EMT) with Cisplatin Resistance.International journal of molecular sciences · 2020Review
- Article
- Tegavivint and the β-Catenin/ALDH Axis in Chemotherapy-Resistant and Metastatic Osteosarcoma.Journal of the National Cancer Institute · 2019Article
- Proteogenomic landscape of squamous cell lung cancer.Nature communications · 2019Article
- miR-340-FHL2 axis inhibits cell growth and metastasis in ovarian cancer.Cell death & disease · 2019Article
- Silencing Transmembrane Protein 45B (TNEM45B) Inhibits Proliferation, Invasion, and Tumorigenesis in Osteosarcoma Cells.Oncology research · 2017Article
- The four and a half LIM domains 2 (FHL2) regulates ovarian granulosa cell tumor progression via controlling AKT1 transcription.Cell death & disease · 2016Article
- Mammalian Actin-binding Protein-1/Hip-55 Interacts with FHL2 and Negatively Regulates Cell Invasion.The Journal of biological chemistry · 2016Article
- B7-H3 protein expression in a murine model of osteosarcoma.Oncology letters · 2016Article
Corrections and comments
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Authors and funding
9 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe molecular mechanisms that are involved in the growth and invasiveness of osteosarcoma, an aggressive and invasive primary bone tumor, are not fully understood. The transcriptional co-factor FHL2 (four and a half LIM domains protein 2) acts as an oncoprotein or as a tumor suppressor depending on the tissue context. In this study, we investigated the role of FHL2 in tumorigenesis in osteosarcoma model. METHODOLOGY/PRINCIPAL
findingsWestern blot analyses showed that FHL2 is expressed above normal in most human and murine osteosarcoma cells. Tissue microarray analysis revealed that FHL2 protein expression is high in human osteosarcoma and correlates with osteosarcoma aggressiveness. In murine osteosarcoma cells, FHL2 silencing using shRNA decreased canonical Wnt/β-catenin signaling and reduced the expression of Wnt responsive genes as well as of the key Wnt molecules Wnt5a and Wnt10b. This effect resulted in inhibition of osteosarcoma cell proliferation, invasion and migration in vitro. Using xenograft experiments, we showed that FHL2 silencing markedly reduced tumor growth and lung metastasis occurence in mice. The anti-oncogenic effect of FHL2 silencing in vivo was associated with reduced cell proliferation and decreased Wnt signaling in the tumors. CONCLUSION/SIGNIFICANCE: Our findings demonstrate that FHL2 acts as an oncogene in osteosarcoma cells and contributes to tumorigenesis through Wnt signaling. More importantly, FHL2 depletion greatly reduces tumor cell growth and metastasis, which raises the potential therapeutic interest of targeting FHL2 to efficiently impact primary bone tumors.
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