ArticleEndocrine-related cancer2016
Angiopoietin-2 promotes ER+ breast cancer cell survival in bone marrow niche.
Article in Endocrine-related cancer, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
17 citing papers in PubMed, 25 citations in OpenAlex.
- Human cytomegalovirus UL82 promotes colorectal cancer cell proliferation through inhibiting the ubiquitination of OGDH via ANGPT2.Tumour virus research · 2025Article
- Review
- Outlook and opportunities for engineered environments of breast cancer dormancy.Science advances · 2024Review
- Article
- Review
- Review
- Osteoblasts and osteoclasts: an important switch of tumour cell dormancy during bone metastasis.Journal of experimental & clinical cancer research : CR · 2022Review
- Effects of metformin on human bone-derived mesenchymal stromal cell-breast cancer cell line interactions.Medical oncology (Northwood, London, England) · 2022Article
- Thorny ground, rocky soil: Tissue-specific mechanisms of tumor dormancy and relapse.Seminars in cancer biology · 2022Review
- Ang2-Targeted Combination Therapy for Cancer Treatment.Frontiers in immunology · 2022Review
- Loss of microRNA-135b Enhances Bone Metastasis in Prostate Cancer and Predicts Aggressiveness in Human Prostate Samples.Cancers · 2021Article
- The Adipokine Component in the Molecular Regulation of Cancer Cell Survival, Proliferation and Metastasis.Pathology oncology research : POR · 2021Review
- Autophagy and Cancer Dormancy.Frontiers in oncology · 2021Review
- The Role of Adipokines and Bone Marrow Adipocytes in Breast Cancer Bone Metastasis.International journal of molecular sciences · 2020Review
- TIE2 Induces Breast Cancer Cell Dormancy and Inhibits the Development of Osteolytic Bone Metastases.Cancers · 2020Article
- Immunosignature Screening for Multiple Cancer Subtypes Based on Expression Rule.Frontiers in bioengineering and biotechnology · 2019Article
- Reawakening of dormant estrogen-dependent human breast cancer cells by bone marrow stroma secretory senescence.Cell communication and signaling : CCS · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In estrogen receptor-positive (ER+) breast cancer, it is recognized that metastases may develop after a long period of dormancy. Bone marrow (BM) vascular niche is where the dormant tumor cells are most likely to reside. So far, it is not fully understood why the dormant tumor cells become proliferative and eventually generate tumor. We hypothesized that therapeutic or menopause-related estrogen depletion may be the switch behind dormant ER+ tumor cell awakening in BM. We utilized an existing experimental model of BM endothelial niche that can simulate ER+ tumor cell dormancy to test our hypothesis. In results, estrogen depletion paradoxically promoted ER+ tumor cell proliferation in the BM endothelial niche, and their molecular phenotype shifted from dormant to awaken. Following estrogen depletion, the BM niche cells produced angiopoietin-2 (ANGPT2), which destabilized niche endothelium by interfering ANGPT1/Tie2 signaling, and promoted ER+ tumor cell survival under estrogen deficiency via cell surface integrin &1. Knockdown of ANGPT2 completely negated ER+ tumor cell awakening in the niche. Furthermore, ANGPT2 expression in ER+ tumor human samples was associated with increased risk of distant metastasis only in those who underwent adjuvant estrogen depletion therapy, not in those who did not undergo adjuvant therapy. In conclusion, we demonstrate that ANGPT2 signaling activated after estrogen depletion paradoxically triggers ER+ tumor cell awakening from dormancy in their BM niche, partly indirectly via endothelial Tie2 receptor and partly directly via tumor cell surface integrin &1.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.