ArticleBritish journal of cancer2025
Androgen receptor interacts with c-Myc to regulate macrophage-osteoclast axis and drive bone metastasis in triple negative breast cancer.
Article in British journal of cancer, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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Who cites it
3 citing papers in PubMed.
- Integrative multi-omic analysis identifiedCancer biology & medicine · 2026Article
- RNA-binding protein RBM47 in health and disease: molecular mechanisms, preclinical evidence, and translational challenges.Frontiers in immunology · 2026Review
- Regulation of Stromal Cells by Sex Steroid Hormones in the Breast Cancer Microenvironment.Cancers · 2024Review
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Authors and funding
9 authors.
Funding
Abstract
backgroundBreast cancer distant metastasis is known to exhibit organotropism, with triple negative breast cancer (TNBC) subtypes also displaying organ-specific metastasis. The precise regulatory mechanisms governing this specificity remain unclear.
methodsRetrospective analysis of metastatic data from public databases was utilized to explore the organotropism of TNBC subtypes. Mouse models combined with single-cell sequencing and immunoprecipitation (CoIP) experiments were utilized to investigate the role and mechanism of androgen receptor (AR) on TNBC bone metastasis. Further analysis of the bone microenvironment combined with CUT&TAG sequencing and osteoclast differentiation experiments was performed to validate the effect of AR and c-Myc interaction on macrophage-osteoclast axis differentiation.
resultsAnalysis revealed the luminal androgen receptor (LAR) TNBC subtype had significant bone metastasis propensity. Mouse models showed AR activation promoted LAR TNBC bone metastasis. Using single-cell sequencing, we discovered that c-Myc played a critical role in AR-mediated bone metastasis. Further investigation of the bone microenvironment showed that AR-c-Myc interaction promoted macrophage-osteoclast axis differentiation and macrophage activation via MMP13, ultimately increasing bone resorption.
conclusionsAR and c-Myc interaction induces macrophage differentiation into osteoclasts and promotes TNBC bone metastasis. These findings elucidate the mechanisms underlying bone metastasis in TNBC subtypes and inform potential interventions for TNBC bone metastasis.
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