ArticleClinical & experimental metastasis2014
RANK expression on breast cancer cells promotes skeletal metastasis.
Article in Clinical & experimental metastasis, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 57 citations in OpenAlex.
- Dynamic changes of Receptor activator of nuclear factor-κB expression in Circulating Tumor Cells during Denosumab predict treatment effectiveness in Metastatic Breast Cancer.Scientific reports · 2020Trial
- Review
- Mechanism and intervention strategy of thymus atrophy in cancer immunotherapy.American journal of cancer research · 2026Review
- Cancer Metastasis: Therapeutic Challenges and Opportunities.Medical oncology (Northwood, London, England) · 2025Review
- Adipocyte-Tumor Interactions in the Bone Marrow Niche: Implications for Metastasis and Therapy.International journal of molecular sciences · 2025Review
- RANKL Drives Bone Metastasis in Mammary Cancer: Protective Effects of Anti-Resorptive Treatments.International journal of molecular sciences · 2025Article
- The osteoblast in regulation of tumor cell dormancy and bone metastasis.Journal of bone oncology · 2024Article
- Predictive and prognostic biomarkers of bone metastasis in breast cancer: current status and future directions.Cell & bioscience · 2023Review
- Co-targeting RANK pathway treats and prevents acquired resistance to CDK4/6 inhibitors in luminal breast cancer.Cell reports. Medicine · 2023Article
- Review
- Key events in cancer: Dysregulation of SREBPs.Frontiers in pharmacology · 2023Review
- The Roadmap of RANKL/RANK Pathway in Cancer.Cells · 2021Review
- Article
- Impact of cholesterol-pathways on breast cancer development, a metabolic landscape.Journal of Cancer · 2021Review
- Expression of receptor activator of NFkB (RANK) drives stemness and resistance to therapy in ER+HER2- breast cancer.Oncotarget · 2020Article
- Targeting MAPK Signaling in Cancer: Mechanisms of Drug Resistance and Sensitivity.International journal of molecular sciences · 2020Review
- Short-term RANKL exposure initiates a neoplastic transcriptional program in the basal epithelium of the murine salivary gland.Cytokine · 2019Article
- Prediction of Bone Metastasis in Inflammatory Breast Cancer Using a Markov Chain Model.The oncologist · 2019Article
- The RANK-RANKL axis: an opportunity for drug repurposing in cancer?Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2019Review
- ERRα promotes breast cancer cell dissemination to bone by increasing RANK expression in primary breast tumors.Oncogene · 2019Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
RANK ligand (RANKL), acting through its cognate receptor RANK, is a key factor for bone remodeling and metastasis by regulating the differentiation, survival and activation of osteoclasts. RANKL is also crucial for the development of mouse mammary glands during pregnancy and has been recently linked to the etiology of breast cancer via its direct activity on RANK-expressing normal or transformed breast epithelial cells, leading to increased mitogenesis, enhanced regenerative potential of mammary stem cells, and increased invasion and migration. We demonstrate that higher RANK expression in MDA-MB-231 breast cancer cells (MDA-231-RANK cells) is sufficient to confer a significantly greater metastatic growth rate in the bone compared with MDA-MB-231 cells which do not express high levels of RANK. Blockade of osteoclastic bone resorption, achieved with treatment by either RANKL inhibition or zoledronic acid, did reduce skeletal tumor progression of MDA-231-RANK cells suggesting that the vicious cycle contributes to metastatic growth. However, RANKL inhibition reduced skeletal growth of MDA-231-RANK tumors to a significantly greater extent than zoledronic acid, indicating that skeletal growth of RANK-positive tumors is also driven by direct RANKL effects. RANKL stimulated the expression of multiple genes associated with cell invasive behavior, including several matrix metalloproteinases and other genes previously defined as part of a bone metastasis gene signature. These data indicate that RANKL provokes breast cancer bone metastases via two distinct, but potentially overlapping mechanisms: stimulation of tumor-associated osteoclastogenesis and stimulation of RANK-expressing tumor cells.
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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.