ArticleOncogene2010
Transcriptome profiling of a TGF-beta-induced epithelial-to-mesenchymal transition reveals extracellular clusterin as a target for therapeutic antibodies.
Article in Oncogene, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 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.
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Who cites it
42 citing papers in PubMed, 80 citations in OpenAlex.
- Identification of the thiol isomerase-binding peptide, mastoparan, as a novel inhibitor of shear-induced transforming growth factor β1 (TGF-β1) activation.The Journal of biological chemistry · 2013Trial
- Article
- Dorsomorphin Suppresses EMT to Reduce AR-Negative Prostate Cancer Metastasis by Synergistically Antagonizing JAK2/STAT3 and Gli2-Independent Shh Activation.Prostate cancer · 2025Article
- Review
- The role and function of CLU in cancer biology and therapy.Clinical and experimental medicine · 2023Review
- Diagnostic and therapeutic biomarkers in colorectal cancer: a review.American journal of cancer research · 2022Review
- Inflammation, Extracellular Matrix Remodeling, and Proteostasis in Tumor Microenvironment.International journal of molecular sciences · 2021Review
- Bioengineering strategies to control epithelial-to-mesenchymal transition for studies of cardiac development and disease.APL bioengineering · 2021Review
- The multiple roles and therapeutic potential of clusterin in non-small-cell lung cancer: a narrative review.Translational lung cancer research · 2021Review
- Hypoxia Upregulates NOTCH3 Signaling Pathway to Promote Endothelial-Mesenchymal Transition in Pulmonary Artery Endothelial Cells.Evidence-based complementary and alternative medicine : eCAM · 2021Article
- The Multiple Roles and Therapeutic Potential of Molecular Chaperones in Prostate Cancer.Cancers · 2019Review
- The Role of Breast Cancer Stem Cells as a Prognostic Marker and a Target to Improve the Efficacy of Breast Cancer Therapy.Cancers · 2019Review
- Reproducibility of novel immune-inflammatory biomarkers over 4 months: an analysis with repeated measures design.Biomarkers in medicine · 2019Article
- The role of Clusterin in cancer metastasis.Cancer management and research · 2019Article
- TGF-β1 induces HMGA1 expression: The role of HMGA1 in thyroid cancer proliferation and invasion.International journal of oncology · 2017Article
- Article
- Exosomes: A Rising Star in Falling Hearts.Frontiers in physiology · 2017Review
- Clusterin signals via ApoER2/VLDLR and induces meiosis of male germ cells.American journal of translational research · 2017Article
- Cardiac Extracellular Vesicles in Normal and Infarcted Heart.International journal of molecular sciences · 2016Review
- Anti-Cancer Stem-like Cell Compounds in Clinical Development - An Overview and Critical Appraisal.Frontiers in oncology · 2016Review
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 2 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Transforming growth factor (TGF)-beta plays a dual role in tumorigenesis, switching from acting as a growth inhibitory tumor suppressor early in the process, to a tumor promoter in late-stage disease. Since TGF-beta's prometastatic role may be linked to its ability to induce tumor cell epithelial-to-mesenchymal transition (EMT), we explored TGF-beta's EMT-promoting pathways by analysing the transcriptome changes occurring in BRI-JM01 mammary tumor epithelial cells undergoing a TGF-beta-induced EMT. We found the clusterin gene to be the most highly upregulated throughout most of the TGF-beta time course, and showed that this results in an increase of the secreted form of clusterin. By monitoring several hallmark features of EMT, we demonstrated that antibodies targeting secreted clusterin inhibit the TGF-beta-induced EMT of BRI-JM01 cells, as well as the invasive phenotype of several other breast and prostate tumor cell lines (4T1, NMuMG, MDA-MB231LM2 and PC3), without affecting the proliferation of these cells. These results indicate that secreted clusterin is a functionally important EMT mediator that lies downstream within TGF-beta's EMT-promoting transcriptional cascade, but not within its growth-inhibitory pathways. To further investigate the role played by secreted clusterin in tumor metastasis, we assessed the effect of several anti-clusterin monoclonal antibodies in vivo using a 4T1 syngeneic mouse breast cancer model and found that these antibodies significantly reduce lung metastasis. Taken together, our results reveal a role for secreted clusterin as an important extracellular promoter of EMT, and suggest that antibodies targeting clusterin may inhibit tumor metastasis without reducing the beneficial growth inhibitory effects of TGF-beta.
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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.