ArticleCell2021
The bone microenvironment invigorates metastatic seeds for further dissemination.
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Article in Cell, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 171 papers.
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171citing papers in PubMed
15.6field-weighted citation impact, top 1% of its field
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Who cites it
171 citing papers in PubMed, 230 citations in OpenAlex.
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- A CTC/DTC-centered temporal framework of bone metastasis: From dissemination to dormancy and reactivation.Journal of bone oncology · 2026Review
- Heterogeneity in cancer: molecular mechanisms and therapeutic strategies.Signal transduction and targeted therapy · 2026Review
- Loss of short-form Ron promotes B and T cell cooperation to prevent outgrowth of breast cancer bone metastasis.bioRxiv : the preprint server for biology · 2026Article
- Spatiotemporal lineage tracing reveals the dynamic spatial architecture of tumor growth and metastasis.Nature genetics · 2026Article
- NF1 loss in estrogen receptor-positive breast cancer induces osteoclast formation and immunosuppression to promote bone metastasis.Cancer letters · 2026Article
- Cytokine Regulation of the Bone Pre- and Metastatic Niches: Implications for Breast Cancer Dormancy.Cells · 2026Review
- Phylogeography of Bone Metastasis: Clonal Evolution, Skeletal Niche Adaptation, and Clinical Implications.International journal of molecular sciences · 2026Review
- Breaking the immune "cold niche" in bone metastasis: core mechanisms of the multidimensional interwoven regulatory network and precision breakthrough strategies.Molecular cancer · 2026Review
- The liver-bone axis: an emerging player in disease pathogenesis and therapeutic intervention.Science China. Life sciences · 2026Review
- Decoding triple negative breast cancer bone metastasis: from 3D bioprinted models to clinical translation.Journal of nanobiotechnology · 2026Review
- LLMs as emerging tools for understanding and managing bone metastasis and cancer-induced bone pain.iScience · 2026Article
- From bone to beyond: osteoclasts dictate metastatic fate in lung adenocarcinoma via the OLFML3-DPPA2 stemness switch.Biology direct · 2026Article
- Article
- Targeting arginine metabolism reverses bone immunosuppressive microenvironment and metastasis in ARID1A-deficient triple negative breast cancer.Nature communications · 2026Article
- Complex I protein NDUFB9 is a metabolic vulnerability in triple negative breast cancer brain metastases.Nature communications · 2026Article
- Using CRISPR barcoding as a molecular clock to capture dynamic processes at single-cell resolution.Genome research · 2026Article
- Molecular subtype concordance and metastatic patterns in muscle-invasive bladder cancer.The journal of pathology. Clinical research · 2026Article
111 more citing papers are in PubMed but not listed here.
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Authors and funding
25 authors at 2 institutions in 1 country.
Weijie ZhangLester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX 77030, USA; Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
Igor L BadoLester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX 77030, USA; Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
Jingyuan HuJan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, TX 77030, USA; Quantitative and Computational Biosciences Program, Baylor College of Medicine, Houston, TX 77030, USA.
Ying-Wooi WanJan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, TX 77030, USA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
Ling WuLester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX 77030, USA; Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
Hai WangLester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX 77030, USA; Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
Yang GaoLester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX 77030, USA; Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
Hyun-Hwan JeongJan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, TX 77030, USA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
Zhan XuLester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX 77030, USA; Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
Xiaoxin HaoLester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX 77030, USA; Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
Bree M LegeLester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
Rami Al-OuranJan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, TX 77030, USA; Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA.
Lucian LiJan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, TX 77030, USA; Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA.
Jiasong LiDepartment of Systems Medicine and Bioengineering and Translational Biophotonics Laboratory, Houston Methodist Cancer Center, Houston, TX 77030, USA.
Liqun YuLester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX 77030, USA; Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
Swarnima SinghLester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX 77030, USA; Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
Hin Ching LoLester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX 77030, USA; Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
Muchun NiuIntegrative Molecular and Biomedical Sciences Graduate Program, Baylor College of Medicine, Houston, TX 77030, USA.
Jun LiuLester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX 77030, USA; Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
Weiyu JiangLester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX 77030, USA; Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
Yi LiLester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX 77030, USA; Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
Stephen T C WongDan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA; Department of Systems Medicine and Bioengineering and Translational Biophotonics Laboratory, Houston Methodist Cancer Center, Houston, TX 77030, USA.
Chonghui ChengLester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
Zhandong LiuJan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, TX 77030, USA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
Xiang H-F ZhangLester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX 77030, USA; Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA; McNair Medical Institute, Baylor College of Medicine, Houston, TX 77030, USA. Electronic address: xiangz@bcm.edu.
Baylor College of Medicine · USHouston Methodist · US
Funding
Tumor BiologyP30CA125123 · NCI · BAYLOR COLLEGE OF MEDICINE · PI DAVID R ROWLEY · 2007 to 2026
$73.9MOsteoclast-Independent Mechanisms of Early-Stage Bone Colonization of Breast CancerR01CA183878 · NCI · BAYLOR COLLEGE OF MEDICINE · PI ZHANG, XIANG · 2014 to 2024
$3.5MSpatiotemporal modeling of cancer-niche interactions in breast cancer bone metastasisU01CA253553 · NCI · METHODIST HOSPITAL RESEARCH INSTITUTE · PI WONG, STEPHEN TC, ZHANG, XIANG · 2020 to 2024
$3.0MUnveiling the mechanisms underlying secondary metastasis and possible therapeutic windowsR01CA251950 · NCI · BAYLOR COLLEGE OF MEDICINE · PI ZHANG, XIANG · 2020 to 2024
$2.6MOsteogenic Niche Biology in Progression and Endocrine Resistance of Bone MetastasesR01CA221946 · NCI · BAYLOR COLLEGE OF MEDICINE · PI ROWLEY, DAVID R · 2018 to 2022
$2.4MRewired Metabolism Regulates Vessel Normalization and ImmunosuppressionR01CA227904 · NCI · BAYLOR COLLEGE OF MEDICINE · PI SREEKUMAR, ARUN, ZHANG, XIANG · 2019 to 2023
$2.3MBD Biosciences Special Order LSRIIS10RR024574 · NCRR · BAYLOR COLLEGE OF MEDICINE · PI LUMPKIN, ELLEN A · 2009 to 2009
$430kTecan EVO GenePaint robotS10OD016167 · OD · BAYLOR COLLEGE OF MEDICINE · PI LJUNGBERG, CECILIA · 2013 to 2013
$215kNCI NIH HHS P30 CA125123NCI NIH HHS R01 CA183878NCI NIH HHS R01 CA221946NCI NIH HHS R01 CA227904NCI NIH HHS R01 CA251950NCI NIH HHS U01 CA253553NCRR NIH HHS S10 RR024574NIH HHS S10 OD016167
Abstract
Metastasis has been considered as the terminal step of tumor progression. However, recent genomic studies suggest that many metastases are initiated by further spread of other metastases. Nevertheless, the corresponding pre-clinical models are lacking, and underlying mechanisms are elusive. Using several approaches, including parabiosis and an evolving barcode system, we demonstrated that the bone microenvironment facilitates breast and prostate cancer cells to further metastasize and establish multi-organ secondary metastases. We uncovered that this metastasis-promoting effect is driven by epigenetic reprogramming that confers stem cell-like properties on cancer cells disseminated from bone lesions. Furthermore, we discovered that enhanced EZH2 activity mediates the increased stemness and metastasis capacity. The same findings also apply to single cell-derived populations, indicating mechanisms distinct from clonal selection. Taken together, our work revealed an unappreciated role of the bone microenvironment in metastasis evolution and elucidated an epigenomic reprogramming process driving terminal-stage, multi-organ metastases.
Indexed as
Neoplasm MetastasisTumor MicroenvironmentAnimalsApoptosisBiomarkers, TumorBone NeoplasmsBreast NeoplasmsCell ProliferationDisease ProgressionFemaleGene Expression ProfilingGene Expression Regulation, NeoplasticHumansMaleMiceMice, Inbred C57BLBiomarkers, Tumorbone metastasiscirculating tumor cellsdisseminated tumor cellsepigenomic reprogramingevolving barcodesEZH2organ tropismplasticitysecondary metastasisstemness
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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.