ArticleProceedings of the National Academy of Sciences of the United States of America2018
HIF signaling in osteoblast-lineage cells promotes systemic breast cancer growth and metastasis in mice.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
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Who cites it
59 citing papers in PubMed.
- RET-driven osteoprotegerin expression links medullary thyroid cancer to osteoblastic bone metastases.Cell reports. Medicine · 2026Article
- Hijacking the bone niche: mechanistic insights into bone metastasis in breast cancer.Bone research · 2026Review
- Prelimbic cortex-basolateral amygdala glutamatergic circuit drives cancer-induced bone pain in mice.iScience · 2026Article
- Microenvironmental and Molecular Pathways Driving Dormancy Escape in Bone Metastases.International journal of molecular sciences · 2025Review
- Investigating the mechanism of Gentiopicroside in rheumatoid arthritis through network pharmacology, molecular docking, and experimental validation.Scientific reports · 2025Article
- Nutrients Lowering Obesity-Linked Chemokines Blamable for Metastasis.International journal of molecular sciences · 2025Review
- The Recruitment and Immune Suppression Mechanisms of Myeloid-Derived Suppressor Cells and Their Impact on Bone Metastatic Cancer.Cancer reports (Hoboken, N.J.) · 2025Review
- Bevacizumab and anlotinib combination therapy acts via HIF-1α suppression to exert synergistic anti-angiogenic and anti-tumor effects in non-small cell lung cancer.Frontiers in immunology · 2025Article
- Tumor-derived extracellular vesicles: key drivers of immunomodulation in breast cancer.Frontiers in immunology · 2025Review
- Activation of the osteoblastic HIF-1α pathway partially alleviates the symptoms of STZ-induced type 1 diabetes mellitus via RegIIIγ.Experimental & molecular medicine · 2024Article
- The osteoblast in regulation of tumor cell dormancy and bone metastasis.Journal of bone oncology · 2024Article
- Multiple influence of immune cells in the bone metastatic cancer microenvironment on tumors.Frontiers in immunology · 2024Review
- Molecular mechanism of bone metastasis in breast cancer.Frontiers in oncology · 2024Review
- The skeleton: an overlooked regulator of systemic glucose metabolism in cancer?Frontiers in oncology · 2024Article
- Mechanisms of Organ-Specific Metastasis of Breast Cancer.Cold Spring Harbor perspectives in medicine · 2023Review
- Organ-Specificity of Breast Cancer Metastasis.International journal of molecular sciences · 2023Review
- Amino Acid Metabolism in Bone Metastatic Disease.Current osteoporosis reports · 2023Review
- SCUBE2 mediates bone metastasis of luminal breast cancer by modulating immune-suppressive osteoblastic niches.Cell research · 2023Article
- Circulating biomarkers for diagnosis and therapeutic monitoring in bone metastasis.Journal of bone and mineral metabolism · 2023Review
- WHIM Syndrome-linked CXCR4 mutations drive osteoporosis.Nature communications · 2023Article
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Authors and funding
10 authors.
Funding
Abstract
Bone metastasis involves dynamic interplay between tumor cells and the local stromal environment. In bones, local hypoxia and activation of the hypoxia-inducible factor (HIF)-1α in osteoblasts are essential to maintain skeletal homeostasis. However, the role of osteoblast-specific HIF signaling in cancer metastasis is unknown. Here, we show that osteoprogenitor cells (OPCs) are located in hypoxic niches in the bone marrow and that activation of HIF signaling in these cells increases bone mass and favors breast cancer metastasis to bone locally. Remarkably, HIF signaling in osteoblast-lineage cells also promotes breast cancer growth and dissemination remotely, in the lungs and in other tissues distant from bones. Mechanistically, we found that activation of HIF signaling in OPCs increases blood levels of the chemokine C-X-C motif ligand 12 (CXCL12), which leads to a systemic increase of breast cancer cell proliferation and dissemination through direct activation of the CXCR4 receptor. Hence, our data reveal a previously unrecognized role of the hypoxic osteogenic niche in promoting tumorigenesis beyond the local bone microenvironment. They also support the concept that the skeleton is an important regulator of the systemic tumor environment.
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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.