ArticleProceedings of the National Academy of Sciences of the United States of America2019
COX-2 mediates tumor-stromal prolactin signaling to initiate tumorigenesis.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 47 citations in OpenAlex.
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- Lentinula edodes Cultured Extract Intake at Puberty Mitigates Inflammatory Signals at the Mammary Glands by the Involvement of Epigenetic Mechanisms in BALB/c Mice.The breast journal · 2026Article
- Circulating tumor cells: Blood-based detection, molecular biology, and clinical applications.Cancer cell · 2025Review
- Nuclear receptors in health and disease: signaling pathways, biological functions and pharmaceutical interventions.Signal transduction and targeted therapy · 2025Review
- Advances in the identification of novel cell signatures in benign prostatic hyperplasia and prostate cancer using single-cell RNA sequencing.Frontiers in immunology · 2025Review
- Synthesis of Novel Benzofuran Spiro-2-Pyrrolidine Derivatives via [3+2] Azomethine Ylide Cycloadditions and Their Antitumor Activity.International journal of molecular sciences · 2024Article
- Amentoflavone alleviated cartilage injury and inflammatory response of knee osteoarthritis through PTGS2.Naunyn-Schmiedeberg's archives of pharmacology · 2024Article
- Rel Family Transcription Factor NFAT5 Upregulates COX2 via HIF-1α Activity in Ishikawa and HEC1a Cells.International journal of molecular sciences · 2024Article
- Rosmarinic acid in combination with ginsenoside Rg1 suppresses colon cancer metastasis via co-inhition of COX-2 and PD1/PD-L1 signaling axis.Acta pharmacologica Sinica · 2024Article
- Article
- The p23 co-chaperone is a succinate-activated COX-2 transcription factor in lung adenocarcinoma tumorigenesis.Science advances · 2023Article
- Review
- Unveiling novel insights in prostate cancer through single-cell RNA sequencing.Frontiers in oncology · 2023Review
- Breast Cancer and Prolactin - New Mechanisms and Models.Endocrinology · 2022Review
- Modulation of the tumor microenvironment by natural agents: implications for cancer prevention and therapy.Seminars in cancer biology · 2022Review
- Prolactin: The Third Hormone in Breast Cancer.Frontiers in endocrinology · 2022Review
- Therapeutic potential of NR4A1 in cancer: Focus on metabolism.Frontiers in oncology · 2022Review
- Physical Forces and Transient Nuclear Envelope Rupture during Metastasis: The Key for Success?Cancers · 2021Review
- Integrated computational analyses reveal novel insights into the stromal microenvironment of SHH-subtype medulloblastoma.Scientific reports · 2021Article
- NR4A1 regulates expression of immediate early genes, suppressing replication stress in cancer.Molecular cell · 2021Article
Corrections and comments
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Authors and funding
21 authors at 3 institutions in 1 country.
Funding
Abstract
Tumor-stromal communication within the microenvironment contributes to initiation of metastasis and may present a therapeutic opportunity. Using serial single-cell RNA sequencing in an orthotopic mouse prostate cancer model, we find up-regulation of prolactin receptor as cancer cells that have disseminated to the lungs expand into micrometastases. Secretion of the ligand prolactin by adjacent lung stromal cells is induced by tumor cell production of the COX-2 synthetic product prostaglandin E2 (PGE2). PGE2 treatment of fibroblasts activates the orphan nuclear receptor NR4A (Nur77), with prolactin as a major transcriptional target for the NR4A-retinoid X receptor (RXR) heterodimer. Ectopic expression of prolactin receptor in mouse cancer cells enhances micrometastasis, while treatment with the COX-2 inhibitor celecoxib abrogates prolactin secretion by fibroblasts and reduces tumor initiation. Across multiple human cancers, COX-2, prolactin, and prolactin receptor show consistent differential expression in tumor and stromal compartments. Such paracrine cross-talk may thus contribute to the documented efficacy of COX-2 inhibitors in cancer suppression.
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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.