ArticleBreast cancer research : BCR2025
Secreted LGALS3BP facilitates distant metastasis of breast cancer.
Article in Breast cancer research : BCR, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed.
- MZT2A drives epithelial-mesenchymal transition in lung adenocarcinoma via the LGALS3BP/ITGB1/TGF-β/smad2 axis.iScience · 2026Article
- dia-PASEF Enables Rapid Profiling of the Human Secretome for Deeper Insights Into Cellular Dynamics and Inflammatory Mechanisms.Molecular & cellular proteomics : MCP · 2026Article
- METTL3 regulates exocytosis independently of mScience advances · 2026Article
- Secretory LGALS3BP exacerbates sepsis-associated liver dysfunction by activating inflammasome-mediated pyroptosis.Cell death discovery · 2026Article
- Multi-omic mapping of Drosophila protein secretomes reveals tissue-specific origins and inter-organ trafficking.Nature communications · 2026Article
- Tamoxifen promotes metastasis of breast cancer via reshaping lipid-driven fibrotic microenvironments in the lung.Neoplasia (New York, N.Y.) · 2026Article
- Glycosylated LGALS3BP is highly secreted by bladder cancer cells and represents a novel urinary disease biomarker.Molecular oncology · 2026Article
- Galectin 3-binding protein suppresses PRRSV replication via Cullin3-mediated ubiquitination degradation of non-structural protein 12.Journal of virology · 2025Article
- LGALS3BP antibody-drug conjugate enhances tumor-infiltrating lymphocytes and synergizes with immunotherapy to restrain neuroblastoma growth.Journal of translational medicine · 2025Article
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12 authors.
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Abstract
backgroundPatients with estrogen receptor (ER)-positive breast cancer (BC) can be treated with endocrine therapy targeting ER, however, metastatic recurrence occurs in 25% of the patients who have initially been treated. Secreted proteins from tumors play important roles in cancer metastasis but previous methods for isolating secretory proteins had limitations in identifying novel targets.
methodsWe applied an in situ secretory protein labeling technique using TurboID to analyze secretome from tamoxifen-resistant (TAMR) BC. The increased expression of LGALS3BP was validated using western blotting, qPCR, ELISA, and IF. Chromatin immunoprecipitation was applied to analyze estrogen-dependent regulation of LGALS3BP transcription. The adhesive and angiogenic functions of LGALS3BP were evaluated by abrogating LGALS3BP expression using either shRNA-mediated knockdown or a neutralizing antibody. Xenograft mouse experiments were employed to assess the in vivo metastatic potential of TAMR cells and the LGALS3BP protein. Clinical evaluation of LGALS3BP risk was carried out with refractory clinical specimens from tamoxifen-treated ER-positive BC patients and publicly available databases.
resultsTAMR secretome analysis revealed that 176 proteins were secreted at least 2-fold more from MCF7/TAMR cells than from sensitive cells, and biological processes such as cell adhesion and angiogenesis were associated with the TAMR secretome. Galectin-3 binding protein (LGALS3BP) was one of the top 10 most highly secreted proteins in the TAMR secretome. The expression level of LGALS3BP was suppressed by estrogen signaling, which involves direct ERα binding to its promoter region. Secreted LGALS3BP in the TAMR secretome helped BC cells adhere to the extracellular matrix and promoted the tube formation of human umbilical vein endothelial cells. Compared with sensitive cells, xenograft animal experiments with MCF7/TAMR cells showed increased pulmonary metastasis, which completely disappeared in LGALS3BP-knockdown TAMR cells. Finally, higher levels of LGALS3BP were associated with poor prognosis in ER-positive BC patients treated with adjuvant tamoxifen in the clinic.
conclusionTAMR secretome analysis identified secretory proteins, such as LGALS3BP, that are involved in biological processes closely related to metastasis. Secreted LGALS3BP from the TAMR cells promoted adhesion of the cells to the extracellular matrix and vasculature formation, which may support metastasis of TAMR cells.
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