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Oligodendrocyte-secreted ERBB3 Mediates the Competitive Uptake of Copper Ions by Tumor Cells to Promote Brain Metastasis in Lung Cancer.

Overview

Authors: Yuechao Yang1,2, Yang Gao1,2, Huanhuan Cui1,2, Sen Li1,2, Zhe Qi1,2, Zhisu Wang1,2, Deheng Li1,2, Lei Chen1,2, Mingtao Feng1,2, Xiaojun Wu1,2, Xin Chen1,2, Bin Hao1,2, Changshuai Zhou1,2, Liangdong Li1,2, Yiqun Cao1,2
  1. Department of Neurosurgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China
  2. Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
Journal: International journal of biological sciences, volume 22, issue 7, pages 3580-3599
Dates: received 22 October 2025; accepted 4 March 2026; published online 25 March 2026
Type: Research article · Language: English
License: CC BY
Identifiers: DOI 10.7150/ijbs.127108 · PMID 42003929 · PMCID PMC13086005 · OpenAlex W7150159800
Open access: gold, a free copy (OpenAlex)
Categories: human (organism), mouse (organism), other condition (population), cellular / molecular (subfield)
Methods: Statistics
Keywords: tumor microenvironment, oligodendrocyte, lung cancer brain metastasis, ERBB3, copper transport
MeSH: Brain Neoplasms*, Copper*, Lung Neoplasms*, Oligodendroglia*, Receptor, erbB-3*, Animals, Cell Line, Tumor, Cell Proliferation, Humans, Mice (* major topic)
Topic: Ferroptosis and cancer prognosis (Cancer Research, Biochemistry, Genetics and Molecular Biology), according to OpenAlex
Citations: cited by 1 paper (Europe PMC); 60 references in the paper
Research resources: H1299 RRID:CVCL_0060, The human NSCLC cell lines H2030 RRID:CVCL_1512, PC9 RRID:CVCL_B260, RRID:CVCL_D357

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.

Reproduced under the paper's license (CC BY), from the paper cited above.

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Data

Datasets cited

Data availability statement

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Reproduced under the paper's license (CC BY), from the paper cited above.

Versions

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Version 1, 30 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 15 authors, 5 keywords, 10 MeSH terms, 60 references, 4 RRIDs.

Cite

This paper

Yang, Y., Gao, Y., Cui, H., Li, S., Qi, Z., Wang, Z., Li, D., Chen, L., Feng, M., Wu, X., Chen, X., Hao, B., Zhou, C., Li, L., & Cao, Y. (2026). Oligodendrocyte-secreted ERBB3 Mediates the Competitive Uptake of Copper Ions by Tumor Cells to Promote Brain Metastasis in Lung Cancer. International journal of biological sciences, 22(7), 3580-3599. https://doi.org/10.7150/ijbs.127108

BibTeX

@article{yang2026oligodendrocyte,
author = {Yang, Yuechao and Gao, Yang and Cui, Huanhuan and Li, Sen and Qi, Zhe and Wang, Zhisu and Li, Deheng and Chen, Lei and Feng, Mingtao and Wu, Xiaojun and Chen, Xin and Hao, Bin and Zhou, Changshuai and Li, Liangdong and Cao, Yiqun},
title = {{Oligodendrocyte-secreted ERBB3 Mediates the Competitive Uptake of Copper Ions by Tumor Cells to Promote Brain Metastasis in Lung Cancer}},
journal = {International journal of biological sciences},
year = {2026},
month = mar,
volume = {22},
number = {7},
pages = {3580--3599},
publisher = {Ivyspring International Publisher},
issn = {1449-2288},
doi = {10.7150/ijbs.127108},
url = {https://doi.org/10.7150/ijbs.127108},
pmid = {42003929},
pmcid = {PMC13086005}
}

RIS

TY - JOUR
AU - Yang, Yuechao
AU - Gao, Yang
AU - Cui, Huanhuan
AU - Li, Sen
AU - Qi, Zhe
AU - Wang, Zhisu
AU - Li, Deheng
AU - Chen, Lei
AU - Feng, Mingtao
AU - Wu, Xiaojun
AU - Chen, Xin
AU - Hao, Bin
AU - Zhou, Changshuai
AU - Li, Liangdong
AU - Cao, Yiqun
TI - Oligodendrocyte-secreted ERBB3 Mediates the Competitive Uptake of Copper Ions by Tumor Cells to Promote Brain Metastasis in Lung Cancer
T2 - International journal of biological sciences
J2 - Int J Biol Sci
PY - 2026
DA - 2026/03/25
VL - 22
IS - 7
SP - 3580
EP - 3599
SN - 1449-2288
PB - Ivyspring International Publisher
DO - 10.7150/ijbs.127108
UR - https://doi.org/10.7150/ijbs.127108
LA - en
ER -

CSL-JSON

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