ArticleBone research2021
Inflammatory conversion of quiescent osteoblasts by metastatic breast cancer cells through pERK1/2 aggravates cancer-induced bone destruction.
Article in Bone research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
What it found
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Who cites it
13 citing papers in PubMed, 18 citations in OpenAlex.
- The Neuro-Bone Axis in Metastatic Progression: Innervation, Neuro-Immune-Osteoclast Crosstalk, and Therapeutic Opportunities.Biology · 2026Review
- Cannabinoid Receptor Type 2 Agonist, GW405833, Reduced the Impacts of MDA-MB-231 Breast Cancer Cells on Bone Cells.Cancer medicine · 2025Article
- Organoids in breast cancer translational research: intersection of technologies.Translational breast cancer research : a journal focusing on translational research in breast cancer · 2025Review
- Article
- Progression of Femoral Osteolytic Metastases after Intramedullary Nailing and Subsequent Salvage Techniques.Cancers · 2024Article
- The Role of Neuromodulation and Potential Mechanism in Regulating Heterotopic Ossification.Neurochemical research · 2024Review
- Recent Advances in Minimally Invasive Management of Osteolytic Periacetabular Skeletal Metastases.Seminars in interventional radiology · 2024Review
- Unique Spatial Transcriptomic Profiling of the Murine Femoral Fracture Callus: A Preliminary Report.Cells · 2024Article
- MicroRNAs mediated interaction of tumor microenvironment cells with breast cancer cells during bone metastasis.Breast cancer (Tokyo, Japan) · 2023Review
- Bone Mass Changes Following Percutaneous Radiofrequency Ablation, Osteoplasty, Reinforcement, and Internal Fixation of Periacetabular Osteolytic Metastases.Journal of clinical medicine · 2023Article
- 3D bioprinted cancer models: from basic biology to drug development.Nature reviews. Cancer · 2022Review
- Muscle and Bone Defects in Metastatic Disease.Current osteoporosis reports · 2022Review
- Treating 'Septic' With Enhanced Antibiotics and 'Arthritis' by Mitigation of Excessive Inflammation.Frontiers in cellular and infection microbiology · 2022Article
Corrections and comments
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Authors and funding
19 authors at 7 institutions in 4 countries.
Funding
Abstract
Disruption of bone homeostasis caused by metastatic osteolytic breast cancer cells increases inflammatory osteolysis and decreases bone formation, thereby predisposing patients to pathological fracture and cancer growth. Alteration of osteoblast function induces skeletal diseases due to the disruption of bone homeostasis. We observed increased activation of pERK1/2 in osteolytic breast cancer cells and osteoblasts in human pathological specimens with aggressive osteolytic breast cancer metastases. We confirmed that osteolytic breast cancers with high expression of pERK1/2 disrupt bone homeostasis via osteoblastic ERK1/2 activation at the bone-breast cancer interface. The process of inflammatory osteolysis modulates ERK1/2 activation in osteoblasts and breast cancer cells through dominant-negative MEK1 expression and constitutively active MEK1 expression to promote cancer growth within bone. Trametinib, an FDA-approved MEK inhibitor, not only reduced breast cancer-induced bone destruction but also dramatically reduced cancer growth in bone by inhibiting the inflammatory skeletal microenvironment. Taken together, these findings suggest that ERK1/2 activation in both breast cancer cells and osteoblasts is required for osteolytic breast cancer-induced inflammatory osteolysis and that ERK1/2 pathway inhibitors may represent a promising adjuvant therapy for patients with aggressive osteolytic breast cancers by altering the shared cancer and bone microenvironment.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.