ArticleInternational journal of oncology2017
Fibulin-4 promotes osteosarcoma invasion and metastasis by inducing epithelial to mesenchymal transition via the PI3K/Akt/mTOR pathway.
Article in International journal of oncology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 55 citations in OpenAlex.
- Fibulin-4 expressed in metastatic breast cancer is a target of peptide-based imaging probes and experimental therapeutics.Molecular therapy. Oncology · 2026Article
- Epithelial-Mesenchymal Transition in Osteosarcoma as a Key Driver of Pulmonary Metastasis.Cancers · 2025Review
- Advancements in Osteosarcoma Therapy: Overcoming Chemotherapy Resistance and Exploring Novel Pharmacological Strategies.Pharmaceuticals (Basel, Switzerland) · 2025Review
- The Role of Epithelial-Mesenchymal Transition in Osteosarcoma Progression: From Biology to Therapy.Diagnostics (Basel, Switzerland) · 2025Review
- Fibulin-4 as a potential extracellular vesicle marker of fibrosis in patients with cirrhosis.FEBS open bio · 2024Article
- Article
- Potassium voltage‑gated channel subfamily E member 4 facilitates the malignant progression of colon cancer by enhancing EGF containing fibulin extracellular matrix protein 2 expression.Experimental and therapeutic medicine · 2023Article
- Deciphering the Signaling Mechanisms of Osteosarcoma Tumorigenesis.International journal of molecular sciences · 2023Review
- EFEMP2 upregulates PD-L1 expression via EGFR/ERK1/2/c-Jun signaling to promote the invasion of ovarian cancer cells.Cellular & molecular biology letters · 2023Article
- Regulation of the Epithelial to Mesenchymal Transition in Osteosarcoma.Biomolecules · 2023Review
- Inflammatory bowel disease-associated intestinal fibrosis.Journal of pathology and translational medicine · 2023Review
- Functional role of MicroRNA/PI3K/AKT axis in osteosarcoma.Frontiers in oncology · 2023Review
- STEAP2 promotes osteosarcoma progression by inducing epithelial-mesenchymal transition via the PI3K/AKT/mTOR signaling pathway and is regulated by EFEMP2.Cancer biology & therapy · 2022Article
- Downregulation of fibulin-4 inhibits autophagy and promotes the sensitivity of esophageal squamous cell carcinoma cells to apatinib by activating the Akt-mTOR signaling pathway.Thoracic cancer · 2022Article
- microRNA-16-5p suppresses cell proliferation and angiogenesis in colorectal cancer by negatively regulating forkhead box K1 to block the PI3K/Akt/mTOR pathway.European journal of histochemistry : EJH · 2022Article
- Identification of key genes as predictive biomarkers for osteosarcoma metastasis using translational bioinformatics.Cancer cell international · 2021Article
- Fibulin 2 Is Hypermethylated and Suppresses Tumor Cell Proliferation through Inhibition of Cell Adhesion and Extracellular Matrix Genes in Non-Small Cell Lung Cancer.International journal of molecular sciences · 2021Article
- Role of Fibulins in Embryonic Stage Development and Their Involvement in Various Diseases.Biomolecules · 2021Review
- Development and analysis of long non-coding RNA-associated competing endogenous RNA network for osteosarcoma metastasis.Hereditas · 2021Article
- Osteosarcoma and Metastasis.Frontiers in oncology · 2021Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
This study explored the role of fibulin-4 in osteosarcoma progression and the possible signaling pathway involved. Fibulin-4 mRNA and protein expression in normal tissue, benign fibrous dysplasia, osteosarcoma, osteosarcoma cell lines, the normal osteoblastic cell line hFOB, and different invasive subclones were evaluated by immunohistochemistry (IHC) or immunocytochemistry (ICC) and real-time reverse transcriptase-polymerase chain reaction (real-time qRT-PCR). Using in vitro functional assays, we analyzed the invasive and proliferative abilities of different osteosarcoma cell lines and subclones with differing invasive potential. To assess the role of fibulin-4 in the invasion and metastasis of osteosarcoma cells, lentiviral vectors with fibulin-4 small hairpin RNA (shRNA) and pLVX-fibulin-4 were constructed and used to infect the highly invasive and low invasive subclones and osteosarcoma cell lines. The effects of fibulin-4 knockdown and upregulation on the biological behavior of osteosarcoma cells were investigated by functional in vitro and in vivo assays. The results revealed that fibulin-4 expression was upregulated in osteosarcoma, and was positively correlated with low differentiation, lymph node metastasis, and poor prognosis. Fibulin-4 was also found to be over-expressed in highly invasive cell lines and in the highly invasive subclones. Fibulin-4 could promote osteosarcoma cell invasion and metastasis by inducing EMT via the PI3K/AKT/mTOR pathway. Collectively, our findings demonstrate that fibulin-4 is a promoter of osteosarcoma development and progression, and suggest a novel therapeutic target for future studies.
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