ArticleBMC cancer2019
CYR61 triggers osteosarcoma metastatic spreading via an IGF1Rβ-dependent EMT-like process.
Article in BMC cancer, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 32 citations in OpenAlex.
- CYR61 Expression Is Induced by IGF1 and Promotes the Proliferation of Prostate Cancer Cells Through the PI3/AKT Signaling Pathway.International journal of molecular sciences · 2025Article
- Targeting metastasis in paediatric bone sarcomas.Molecular cancer · 2025Review
- C-terminal binding protein-2 triggers CYR61-induced metastatic dissemination of osteosarcoma in a non-hypoxic microenvironment.Journal of experimental & clinical cancer research : CR · 2025Article
- Expression of E-cadherin and N-cadherin in Epithelial-to-Mesenchymal Transition of Osteosarcoma: A Systematic Review.Cureus · 2023Review
- CircUSP48 promotes malignant behavior by regulating CYR61 via miR-365 in osteosarcoma.Functional & integrative genomics · 2023Article
- Regulation of the Epithelial to Mesenchymal Transition in Osteosarcoma.Biomolecules · 2023Review
- Assessing the epithelial-to-mesenchymal plasticity in a small cell lung carcinoma (SCLC) and lung fibroblasts co-culture model.Frontiers in molecular biosciences · 2023Article
- Osteosarcoma-Specific Genes as a Diagnostic Tool and Clinical Predictor of Tumor Progression.Biology · 2022Article
- CCN proteins in the musculoskeletal system: current understanding and challenges in physiology and pathology.Journal of cell communication and signaling · 2021Review
- MicroRNA-550a-3-5p controls the brain metastasis of lung cancer by directly targeting YAP1.Cancer cell international · 2021Article
- Review
- SOCS2 is a potential prognostic marker that suppresses the viability of hepatocellular carcinoma cells.Oncology letters · 2021Article
- Molecular Mechanisms of Canine Osteosarcoma Metastasis.International journal of molecular sciences · 2021Review
- Novel Regulators of the IGF System in Cancer.Biomolecules · 2021Review
- Development and validation of an immune gene-set based prognostic signature for soft tissue sarcoma.BMC cancer · 2021Article
- Osteosarcoma and Metastasis.Frontiers in oncology · 2021Review
- Siglec-15 Promotes Tumor Progression in OsteosarcomaFrontiers in oncology · 2021Article
- Down-regulation of PRR11 affects the proliferation, migration and invasion of osteosarcoma by inhibiting the Wnt/β-catenin pathway.Journal of Cancer · 2021Article
- Differential gene expression in cisplatin-resistant and -sensitive testicular germ cell tumor cell lines.Oncotarget · 2020Article
- Pancreatic neuroendocrine tumors: Therapeutic challenges and research limitations.World journal of gastroenterology · 2020Review
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Authors and funding
6 authors at 4 institutions in 2 countries.
Funding
Abstract
backgroundOsteosarcoma is the most prevalent primary bone malignancy in children and young adults. These tumors are highly metastatic, leading to poor outcome. We previously demonstrated that Cysteine-rich protein 61 (CYR61/CCN1) expression level is correlated to osteosarcoma aggressiveness in preclinical model and in patient tumor samples. The aim of the present study was to investigate the CYR61-induced intracellular mechanisms leading to the acquisition of an invasive phenotype by osteosarcoma cells.
methodsModified murine and human osteosarcoma cell lines were evaluated for cell adhesion, aggregation (spheroid), motility (wound healing assay), phenotypic markers expression (RT-qPCR, western blot). Cell-derived xenograft FFPE samples and patients samples (TMA) were assessed by IHC.
resultsCYR61 levels controlled the expression of markers related to an Epithelial-mesenchymal transition (EMT)-like process, allowing tumor cells to migrate acquiring a competent morphology, and to be able to invade the surrounding stroma. This phenotypic shift indeed correlated with tumor grade and aggressiveness in patient samples and with the metastatic dissemination potential in cell-derived xenograft models. Unlike EGFR or PDGFR, IGF1Rβ levels correlated with CYR61 and N-cadherin levels, and with the aggressiveness of osteosarcoma and overall survival. The expression levels of IGF1Rβ/IGF1 axis were controlled by CYR61, and anti-IGF1 neutralizing antibody prevented the CYR61-induced phenotypic shift, aggregation, and motility abilities.
conclusionsTaken together, our study provides new evidence that CYR61 acts as a key inducing factor in the metastatic progression of osteosarcoma by playing a critical role in primary tumor dissemination, with a process associated with IGF1/IGFR stimulation. This suggests that CYR61 may represent a potential pivotal target for therapeutic management of metastases spreading in osteosarcoma, in correlation with IGF1/IGFR pathway.
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