Trial reportThe Journal of clinical investigation2020
Stiff stroma increases breast cancer risk by inducing the oncogene ZNF217.
Trial report in The Journal of clinical investigation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 85 papers.
What it found
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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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
85 citing papers in PubMed, 119 citations in OpenAlex.
- Low-dose tamoxifen treatment reduces collagen organisation indicative of tissue stiffness in the normal breast: results from the KARISMA randomised controlled trial.Breast cancer research : BCR · 2024Trial
- Matrix stiffness-induced YEATS2 drives HCC progression via epigenetic activation of the TGFBR2-TAZ-AKT pathway.Cell death and differentiation · 2026Article
- Tumor-on-chip as a personalized platform for rapid drug testing in breast cancer.Cell reports. Medicine · 2026Article
- The transcription factor ZNF217 drives hepatocellular carcinoma progression by activating de novo lipid synthesis via FASN upregulation.Journal of cancer research and clinical oncology · 2026Article
- The Interplay Between Circadian Clocks and the Tumour Microenvironment in Breast Cancer.Cancers · 2026Review
- Developing virtual physiology of human tumor tissue for malignancy assessment.NPJ precision oncology · 2026Article
- Associations of local breast density with patient characteristics and risk of breast cancer among women undergoing diagnostic breast biopsy.Breast cancer research : BCR · 2026Article
- The Complex Path from Mammary Ductal Hyperplasia to Breast Cancer: Elevated Malignancy Risk in Atypical Forms.Biomedicines · 2026Review
- Increased Toll-Like Receptor-4 Signalling in Breast Tissue of High Fibroglandular Density.Journal of mammary gland biology and neoplasia · 2026Article
- The role of extracellular matrix stiffness in regulating fibroblast behaviors and disease progression.Frontiers in immunology · 2026Review
- Multi-omics investigation reveals molecular determinants of cancer cell evolution on soft extracellular matrix.bioRxiv : the preprint server for biology · 2025Article
- ZNF217 promotes ovarian cancer progression by impacting multiple pivotal steps in the metastatic process.NPJ precision oncology · 2025Article
- Development of breast-mimicking phantoms for use in optical coherence elastography.Journal of biomedical optics · 2025Article
- Article
- Matrix stiffness drives alterations in aldehyde metabolism, inducing DNA damage and transformation.Scientific reports · 2025Article
- Tissue mechanics in tumor heterogeneity and aggression.Trends in cancer · 2025Review
- Extracellular Matrix Signaling Cues: Biological Functions, Diseases, and Therapeutic Targets.MedComm · 2025Review
- Extracellular matrix stiffness in endometrial cancer: driving progression and modulating treatment sensitivity via the ROCK1/YAP1 axis.Cell death & disease · 2025Article
- Mechanisms of breast cancer metastasis: the role of extracellular matrix.Molecular and cellular biochemistry · 2025Review
- Local soft niches in mechanically heterogeneous primary tumors promote brain metastasis via mechanotransduction-mediated HDAC3 activity.Science advances · 2025Article
25 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
22 authors at 9 institutions in 1 country.
Funding
Abstract
Women with dense breasts have an increased lifetime risk of malignancy that has been attributed to a higher epithelial density. Quantitative proteomics, collagen analysis, and mechanical measurements in normal tissue revealed that stroma in the high-density breast contains more oriented, fibrillar collagen that is stiffer and correlates with higher epithelial cell density. microRNA (miR) profiling of breast tissue identified miR-203 as a matrix stiffness-repressed transcript that is downregulated by collagen density and reduced in the breast epithelium of women with high mammographic density. Culture studies demonstrated that ZNF217 mediates a matrix stiffness- and collagen density-induced increase in Akt activity and mammary epithelial cell proliferation. Manipulation of the epithelium in a mouse model of mammographic density supported a causal relationship between stromal stiffness, reduced miR-203, higher levels of the murine homolog Zfp217, and increased Akt activity and mammary epithelial proliferation. ZNF217 was also increased in the normal breast epithelium of women with high mammographic density, correlated positively with epithelial proliferation and density, and inversely with miR-203. The findings identify ZNF217 as a potential target toward which preexisting therapies, such as the Akt inhibitor triciribine, could be used as a chemopreventive agent to reduce cancer risk in women with high mammographic density.
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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.