ArticleInternational journal of biological sciences2026
Oligodendrocyte-secreted ERBB3 Mediates the Competitive Uptake of Copper Ions by Tumor Cells to Promote Brain Metastasis in Lung Cancer.
Article in International journal of biological sciences, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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Who cites it
2 citing papers in PubMed.
- Methyltransferase-like 7B promotes M2-like macrophage polarization in lung adenocarcinoma via upregulating human epidermal growth factor receptor 3 expression and secretion.Oncology letters · 2026Article
- Single-cell and spatial transcriptomes reveal oligodendrocyte remodeling fatty acid metabolism microenvironment of lung cancer brain metastases.Journal of translational medicine · 2026Article
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15 authors.
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Abstract
Recent evidence establishes the brain metastatic microenvironment as a key regulator of metastatic outgrowth, with oligodendrocytes being established as essential components of the brain metastatic microenvironment. Nonetheless, the mechanisms underlying oligodendrocyte-mediated brain metastasis in lung cancer await clarification. Using orthogonal experimental models spanning clinical specimens and animal models, we investigated the presence and functional roles of oligodendrocytes in lung cancer brain metastasis (LCBM). Combinatorial approaches including scRNA-seq, functional genomics, and mechanistic studies revealed ERBB3 as the critical paracrine factor mediating oligodendrocyte-tumor crosstalk. Through comprehensive analysis, we demonstrated the infiltration of oligodendrocytes in the metastatic niche of LCBM. Functional assays demonstrated that oligodendrocytes significantly enhanced the proliferation, migration, and invasion of brain metastatic cells of lung cancer. Mechanistically, oligodendrocyte-secreted ERBB3 acts as a copper chaperone that competitively mobilizes extracellular copper ions through high-affinity binding to SLC31A1 on tumor cells, thereby promoting intracellular copper accumulation. Additionally, elevated ERBB3 expression in LCBM clinical specimens correlated with significantly reduced overall survival and targeted ERBB3 suppressed lung cancer brain metastasis. Our findings establish oligodendrocyte-derived ERBB3 as a critical mediator of intercellular copper transfer via SLC31A1 binding, which coordinately drives brain metastasis progression. Therapeutic targeting of this copper signaling axis represents a promising strategy against LCBM.
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