ArticlePloS one2013
RANKL/RANK/MMP-1 molecular triad contributes to the metastatic phenotype of breast and prostate cancer cells in vitro.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
49 citing papers in PubMed, 1 synthesis or guideline pooled it, 74 citations in OpenAlex.
- Genetics of breast cancer bone metastasis: a sequential multistep pattern.Clinical & experimental metastasis · 2014Pooled it
- 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
- Receptor activator of nuclear factor kappa B (RANK) expression in primary breast cancer correlates with recurrence-free survival and development of bone metastases in I-SPY1 (CALGB 150007/150012; ACRIN 6657).Breast cancer research and treatment · 2017Trial
- Mechanical Loading of Osteocytes via Oscillatory Fluid Flow Regulates Early-Stage PC-3 Prostate Cancer Metastasis to Bone.Advanced biology · 2025Article
- Proteases and Osteoporosis: A Comprehensive Review of Their Role in Bone Health.Current drug targets · 2025Review
- The progressive trend of modeling and drug screening systems of breast cancer bone metastasis.Journal of biological engineering · 2024Review
- The RANK-RANKL-OPG System: A Multifaceted Regulator of Homeostasis, Immunity, and Cancer.Medicina (Kaunas, Lithuania) · 2023Review
- Co-targeting RANK pathway treats and prevents acquired resistance to CDK4/6 inhibitors in luminal breast cancer.Cell reports. Medicine · 2023Article
- Effects of Epigallocatechin-3-Gallate on Matrix Metalloproteinases in Terms of Its Anticancer Activity.Molecules (Basel, Switzerland) · 2023Review
- Capecitabine inhibits epithelial-to-mesenchymal transition and proliferation of colorectal cancer cells by mediating the RANK/RANKL pathway.Oncology letters · 2022Article
- Molecular Mechanisms Leading from Periodontal Disease to Cancer.International journal of molecular sciences · 2022Review
- The Signaling Pathways Associated With Breast Cancer Bone Metastasis.Frontiers in oncology · 2022Review
- Exploring new pathways in endocrine-resistant breast cancer.Exploration of targeted anti-tumor therapy · 2022Review
- Review
- Bone Metastatic Breast Cancer: Advances in Cell Signaling and Autophagy Related Mechanisms.Cancers · 2021Review
- Article
- The Roadmap of RANKL/RANK Pathway in Cancer.Cells · 2021Review
- Article
- The Role of the RANKL/RANK Axis in the Prevention and Treatment of Breast Cancer with Immune Checkpoint Inhibitors and Anti-RANKL.International journal of molecular sciences · 2020Review
- Cellular and Molecular Progression of Prostate Cancer: Models for Basic and Preclinical Research.Cancers · 2020Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 4 institutions in 3 countries.
Funding
Abstract
The osteolytic nature of bone metastasis results from a tumor-driven increased bone resorption. Bone remodeling is orchestrated by the molecular triad RANK-RANKL-OPG. This process is dysregulated in bone metastases, mostly via induction of RANKL by tumor-derived factors. These factors increase expression of RANKL, which induce osteoclast formation, function, and survival, thereby increasing bone resorption. RANK is unexpectedly expressed by cancer cells, and the activation of RANKL-RANK pathway correlates with an increased invasive phenotype. To investigate the interaction between RANK expression in human breast and prostate cancer cells and their pro-metastatic phenotype we analyzed the activation of RANKL-RANK pathway and its effects on cell migration, invasion, gene expression in vitro, and osteolysis-inducing ability in vivo. RANKL activates kinase signaling pathways, stimulates cell migration, increases cell invasion, and up-regulates MMP-1 expression. In vivo, MMP-1 knockdown resulted in smaller x-ray osteolytic lesions and osteoclastogenesis, and decreased tumor burden. Therefore, RANKL inhibition in bone metastatic disease may decrease the levels of the osteoclastogenesis inducer MMP-1, contributing to a better clinical outcome.
Indexed as
Identifiers
What OpenQuestion holds
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.