ArticleInternational journal of biological sciences2022
Poly (ADP-ribose) polymerase 1 (PARP1) inhibition promotes pulmonary metastasis of osteosarcoma by boosting ezrin phosphorylation.
Article in International journal of biological sciences, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 9 citations in OpenAlex.
- SUMOylation is destined for regulatory T cell-related immune dysregulation.Cell death discovery · 2026Review
- Long non-coding RNA NR2F1-AS1: an increasingly significant LncRNA in human cancers.Journal of physiology and biochemistry · 2025Review
- High matrix stiffness accelerates migration of hepatocellular carcinoma cells through the integrin β1-Plectin-F-actin axis.BMC biology · 2025Article
- Advances in non-apoptotic regulated cell death: implications for malignant tumor treatment.Frontiers in oncology · 2025Review
- Review
- DNA Methylation Malleability and Dysregulation in Cancer Progression: Understanding the Role of PARP1.Biomolecules · 2022Review
- PROTAC Degraders with Ligands Recruiting MDM2 E3 Ubiquitin Ligase: An Updated Perspective.Acta materia medica · 2022Article
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
Due to the large proportion of BRCA deficiency and chromosomal instability in OS patients, poly (ADP-ribose) polymerase inhibitors (PARPi) could be an effective strategy for anti-OS therapy. In two orthotopic OS mouse models, we discovered that although PARPi had inhibitory effect on the growth of the orthotopic OS tumors regardless of BRCA deficiency, the treatment of PARPi essentially aggravated the pulmonary metastasis of OS in both models. A protein playing a crucial role in OS metastasis, ezrin, was identified as an interactive protein for PARP1. The phosphorylation of ezrin was significantly promoted during PARP inhibition. Besides the traditional function of phosphorylated ezrin at plasma membrane, we newly identified its nuclear speckle localization and its function with mRNA export. Ezrin knockdown or phosphorylation inhibition could partially rescue PARPi induced metastasis. Collectively, we unveiled a new mechanism for PARP-involved OS metastasis, which proposed a novel combinational therapy strategy using PARP and ezrin inhibitors for future OS treatment.
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