ArticleOncogene2020
Notch3 promotes prostate cancer-induced bone lesion development via MMP-3.
Article in Oncogene, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
36 citing papers in PubMed, 1 synthesis or guideline pooled it, 43 citations in OpenAlex.
- Current evidence on the relationships among five polymorphisms in the matrix metalloproteinases genes and prostate cancer risk.Scientific reports · 2024Pooled it
- Research advances in the role of osteoblasts and their derivatives in the development, recurrence, and distant metastasis of malignant bone tumors: a narrative review.EFORT open reviews · 2025Review
- MMP3 at the crossroads: Linking molecular pathways to disease diagnosis and therapy.Pharmacological research · 2025Review
- [Efficient capture and proteomics analysis of urinary extracellular vesicles by affinity purification].Se pu = Chinese journal of chromatography · 2025Article
- Prostate Cancer Bone Metastasis: Molecular Mechanisms of Tumor and Bone Microenvironment.Cancer management and research · 2025Review
- The role and mechanisms of exosome microRNA in regulating metastasis within the tumor microenvironment of prostate cancer.Frontiers in oncology · 2025Review
- Prostate Cancer Progression Modeling Provides Insight into Dynamic Molecular Changes Associated with Progressive Disease States.Cancer research communications · 2024Article
- Microfluidic Applications in Prostate Cancer Research.Micromachines · 2024Review
- Notch signaling pathway in cancer: from mechanistic insights to targeted therapies.Signal transduction and targeted therapy · 2024Review
- Article
- NOTCH3 promotes docetaxel resistance of prostate cancer cells through regulating TUBB3 and MAPK signaling pathway.Cancer science · 2024Article
- Identification of Molecular Markers Associated with Prostate Cancer Subtypes: An Integrative Bioinformatics Approach.Biomolecules · 2024Article
- Application of dental pulp stem cells for bone regeneration.Frontiers in medicine · 2024Review
- Antagonizing exosomal miR-18a-5p derived from prostate cancer cells ameliorates metastasis-induced osteoblastic lesions by targeting Hist1h2bc and activating Wnt/β-catenin pathway.Genes & diseases · 2023Article
- MTA2 is one of 14 Transcription factors predicting recurrence free survival in gastric cancer and promotes cancer progression by targeting MCM5.Journal of Cancer · 2023Article
- Animal models of cancer metastasis to the bone.Frontiers in oncology · 2023Review
- Consistent DNA Hypomethylations in Prostate Cancer.International journal of molecular sciences · 2022Article
- Sanyin Formula Enhances the Therapeutic Efficacy of Paclitaxel in Triple-Negative Breast Cancer Metastases through the JAK/STAT3 Pathway in Mice.Pharmaceuticals (Basel, Switzerland) · 2022Article
- A statistical physics approach for disease module detection.Genome research · 2022Article
- Advancing Treatment of Bone Metastases through Novel Translational Approaches Targeting the Bone Microenvironment.Cancers · 2022Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
Prostate cancer metastases primarily localize in the bone where they induce a unique osteoblastic response. Elevated Notch activity is associated with high-grade disease and metastasis. To address how Notch affects prostate cancer bone lesions, we manipulated Notch expression in mouse tibia xenografts and monitored tumor growth, lesion phenotype, and the bone microenvironment. Prostate cancer cell lines that induce mixed osteoblastic lesions in bone expressed 5-6 times more Notch3, than tumor cells that produce osteolytic lesions. Expression of active Notch3 (NICD3) in osteolytic tumors reduced osteolytic lesion area and enhanced osteoblastogenesis, while loss of Notch3 in osteoblastic tumors enhanced osteolytic lesion area and decreased osteoblastogensis. This was accompanied by a respective decrease and increase in the number of active osteoclasts and osteoblasts at the tumor-bone interface, without any effect on tumor proliferation. Conditioned medium from NICD3-expressing cells enhanced osteoblast differentiation and proliferation in vitro, while simultaneously inhibiting osteoclastogenesis. MMP-3 was specifically elevated and secreted by NICD3-expressing tumors, and inhibition of MMP-3 rescued the NICD3-induced osteoblastic phenotypes. Clinical osteoblastic bone metastasis samples had higher levels of Notch3 and MMP-3 compared with patient matched visceral metastases or osteolytic metastasis samples. We identified a Notch3-MMP-3 axis in human prostate cancer bone metastases that contributes to osteoblastic lesion formation by blocking osteoclast differentiation, while also contributing to osteoblastogenesis. These studies define a new role for Notch3 in manipulating the tumor microenvironment in bone metastases.
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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.