ArticleDevelopmental cell2021
RANK links senescence to stemness in the mammary epithelia, delaying tumor onset but increasing tumor aggressiveness.
Article in Developmental cell, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 41 citations in OpenAlex.
- Review
- Induction of senescence during postpartum mammary gland involution supports tissue remodeling and promotes postpartum tumorigenesis.Nature aging · 2026Article
- Rank signaling drives basal cell-lineage infidelity leading to mammary tumorigenesis.Nature communications · 2026Article
- Review
- Breast cancer pathogenesis, diagnosis and treatment: a comprehensive review.Frontiers in oncology · 2026Review
- Breast cancer: pathogenesis and treatments.Signal transduction and targeted therapy · 2025Review
- Phytochemical Profile and Biological Activities of the EndemicMolecules (Basel, Switzerland) · 2025Article
- RANK/RANKL Signaling Pathway in Breast Development and Cancer.Advances in experimental medicine and biology · 2025Review
- The crosstalk between senescence, tumor, and immunity: molecular mechanism and therapeutic opportunities.MedComm · 2025Review
- SenNet recommendations for detecting senescent cells in different tissues.Nature reviews. Molecular cell biology · 2024Review
- Review
- RANKL/RANK signaling recruits Tregs via the CCL20-CCR6 pathway and promotes stemness and metastasis in colorectal cancer.Cell death & disease · 2024Article
- Article
- Cellular senescence: Neither irreversible nor reversible.The Journal of experimental medicine · 2024Article
- Dietary restriction in senolysis and prevention and treatment of disease.Critical reviews in food science and nutrition · 2024Review
- Luminal Rank loss decreases cell fitness leading to basal cell bipotency in parous mammary glands.Nature communications · 2023Article
- The Evolving Pathways of the Efficacy of and Resistance to CDK4/6 Inhibitors in Breast Cancer.Cancers · 2023Review
- The RANK-RANKL-OPG System: A Multifaceted Regulator of Homeostasis, Immunity, and Cancer.Medicina (Kaunas, Lithuania) · 2023Review
- Co-targeting RANK pathway treats and prevents acquired resistance to CDK4/6 inhibitors in luminal breast cancer.Cell reports. Medicine · 2023Article
- Imagine beyond: recent breakthroughs and next challenges in mammary gland biology and breast cancer research.Journal of mammary gland biology and neoplasia · 2023Review
Corrections and comments
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Authors and funding
20 authors at 7 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Rank signaling enhances stemness in mouse and human mammary epithelial cells (MECs) and mediates mammary tumor initiation. Mammary tumors initiated by oncogenes or carcinogen exposure display high levels of Rank and Rank pathway inhibitors have emerged as a new strategy for breast cancer prevention and treatment. Here, we show that ectopic Rank expression in the mammary epithelia unexpectedly delays tumor onset and reduces tumor incidence in the oncogene-driven Neu and PyMT models. Mechanistically, we have found that ectopic expression of Rank or exposure to Rankl induces senescence, even in the absence of other oncogenic mutations. Rank leads to DNA damage and senescence through p16/p19. Moreover, RANK-induced senescence is essential for Rank-driven stemness, and although initially translates into delayed tumor growth, eventually promotes tumor progression and metastasis. We uncover a dual role for Rank in the mammary epithelia: Rank induces senescence and stemness, delaying tumor initiation but increasing tumor aggressiveness.
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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.