ArticleCell research2023
SCUBE2 mediates bone metastasis of luminal breast cancer by modulating immune-suppressive osteoblastic niches.
Article in Cell research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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Who cites it
53 citing papers in PubMed, 58 citations in OpenAlex.
- Clinical efficacy and therapy response prediction of neoadjuvant dalpiciclib plus letrozole in postmenopausal patients with HR+/HER2- stage II-III breast cancer (DARLING 01): a single-arm, open-label, exploratory study.Breast cancer research : BCR · 2025Trial
- Prognostic analysis of percutaneous vertebroplasty (PVP) combined withWorld journal of surgical oncology · 2023Trial
- A CTC/DTC-centered temporal framework of bone metastasis: From dissemination to dormancy and reactivation.Journal of bone oncology · 2026Review
- TFF1-mediated suppression of the TCA cycle promotes bone metastasis in triple-negative breast cancer.Translational oncology · 2026Article
- Phylogeography of Bone Metastasis: Clonal Evolution, Skeletal Niche Adaptation, and Clinical Implications.International journal of molecular sciences · 2026Review
- Tumor heterogeneity: development, mechanisms, and therapeutic implications.Signal transduction and targeted therapy · 2026Review
- Breaking the immune "cold niche" in bone metastasis: core mechanisms of the multidimensional interwoven regulatory network and precision breakthrough strategies.Molecular cancer · 2026Review
- Hijacking the bone niche: mechanistic insights into bone metastasis in breast cancer.Bone research · 2026Review
- Targeting arginine metabolism reverses bone immunosuppressive microenvironment and metastasis in ARID1A-deficient triple negative breast cancer.Nature communications · 2026Article
- The Osteoblastic Microenvironment Determines the Fate of Breast Cancer Cells Disseminated in the Bone Marrow.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- ATM promotes bone metastatic propensity of breast cancer by inducing osteoclastogenesis via the NFκB-CCL2 pathway.Acta pharmacologica Sinica · 2026Article
- Review
- Remodeling the tumor dormancy ecosystem to prevent recurrence and metastasis.Signal transduction and targeted therapy · 2026Review
- Analysis of the heterogeneity of the immune microenvironment of bone metastases and new strategies of nanotechnology intervention.Oncology reviews · 2026Review
- Targeting the tripartite axis of immune-metabolic-spatial crosstalk to overcome therapy resistance in breast cancer.Frontiers in immunology · 2026Review
- Mechanical Microenvironment in Tumor Immune Evasion: Bidirectional Regulation Between Matrix Stiffness and Immune Cells and Its Therapeutic Implications.International journal of biological sciences · 2026Review
- [Research Advances on the Immune Evasion Mechanisms of Disseminated Tumor Cells and Their Roles in Cancer Metastasis].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2025Review
- Research advances in the role of osteoblasts and their derivatives in the development, recurrence, and distant metastasis of malignant bone tumors: a narrative review.EFORT open reviews · 2025Review
- Global trends in breast cancer bone metastasis research (2009-2024): a bibliometric and visual analysis of hotspots and future directions.Discover oncology · 2025Article
- The interplay of estrogen, gut microbiome, and bone immunity in osteoporosis.Cell communication and signaling : CCS · 2025Review
Corrections and comments
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Authors and funding
17 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Estrogen receptor (ER)-positive luminal breast cancer is a subtype with generally lower risk of metastasis to most distant organs. However, bone recurrence occurs preferentially in luminal breast cancer. The mechanisms of this subtype-specific organotropism remain elusive. Here we show that an ER-regulated secretory protein SCUBE2 contributes to bone tropism of luminal breast cancer. Single-cell RNA sequencing analysis reveals osteoblastic enrichment by SCUBE2 in early bone-metastatic niches. SCUBE2 facilitates release of tumor membrane-anchored SHH to activate Hedgehog signaling in mesenchymal stem cells, thus promoting osteoblast differentiation. Osteoblasts deposit collagens to suppress NK cells via the inhibitory LAIR1 signaling and promote tumor colonization. SCUBE2 expression and secretion are associated with osteoblast differentiation and bone metastasis in human tumors. Targeting Hedgehog signaling with Sonidegib and targeting SCUBE2 with a neutralizing antibody both effectively suppress bone metastasis in multiple metastasis models. Overall, our findings provide a mechanistic explanation for bone preference in luminal breast cancer metastasis and new approaches for metastasis treatment.
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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.