ArticleOncogenesis2020
Blood platelets stimulate cancer extravasation through TGFβ-mediated downregulation of PRH/HHEX.
Article in Oncogenesis, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
What it found
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Who cites it
21 citing papers in PubMed, 29 citations in OpenAlex.
- Platelet-derived mitochondrial transfer in cancer metastasis: mechanisms, functional consequences, and translational opportunities.Clinical & experimental metastasis · 2026Review
- Article
- Platelet-Prostate cancer crosstalk driving disparities and therapeutic vulnerabilities.Discover oncology · 2026Review
- TGF-β in tumor development and progression: mechanisms and therapeutics.Molecular biomedicine · 2026Review
- Article
- The Duality of Collagens in Metastases of Solid Tumors.International journal of molecular sciences · 2025Review
- Microfluidic Applications in Prostate Cancer Research.Micromachines · 2024Review
- Impact of cell plasticity on prostate tumor heterogeneity and therapeutic response.American journal of clinical and experimental urology · 2024Review
- Prostate cancer cell-platelet bidirectional signaling promotes calcium mobilization, invasion and apoptotic resistance via distinct receptor-ligand pairs.Scientific reports · 2023Article
- The Haematopoietically-expressed homeobox transcription factor: roles in development, physiology and disease.Frontiers in immunology · 2023Review
- Article
- Emerging roles of platelets in cancer biology and their potential as therapeutic targets.Frontiers in oncology · 2022Review
- Preoperative Platelet Count Correlates With Postoperative Perineural Invasion on Specimen in Patients Treated With Radical Prostatectomy.Frontiers in oncology · 2022Article
- Minimal Residual Disease, Metastasis and Immunity.Biomolecules · 2021Review
- Steps in metastasis: an updated review.Medical oncology (Northwood, London, England) · 2021Review
- The Role of Platelet Cell Surface P-Selectin for the Direct Platelet-Tumor Cell Contact During Metastasis Formation in Human Tumors.Frontiers in oncology · 2021Review
- Bidirectional Interaction Between Cancer Cells and Platelets Provides Potential Strategies for Cancer Therapies.Frontiers in oncology · 2021Review
- Pancreatic Cancer and Platelets Crosstalk: A Potential Biomarker and Target.Frontiers in cell and developmental biology · 2021Review
- Article
- The NKL-code for innate lymphoid cells reveals deregulated expression of NKL homeobox genes HHEX and HLX in anaplastic large cell lymphoma (ALCL).Oncotarget · 2020Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Cancer cells go through a process known as epithelial-mesenchymal transition (EMT) during which they acquire the ability to migrate and invade extracellular matrix. Some cells also acquire the ability to move across a layer of endothelial cells to enter and exit the bloodstream; intra- and extravasation, respectively. The transcription factor PRH/HHEX (proline-rich homeodomain/haematopoietically expressed homeobox) controls cell proliferation and cell migration/invasion in a range of cell types. Our previous work showed that PRH activity is downregulated in prostate cancer cells owing to increased inhibitory PRH phosphorylation and that this increases cell proliferation and invasion. PRH inhibits migration and invasion by prostate and breast epithelial cells in part by activating the transcription of Endoglin, a transforming growth factor β (TGFβ) co-receptor. Here we show that depletion of PRH in immortalised prostate epithelial cells results in increased extravasation in vitro. We show that blood platelets stimulate extravasation of cells with depleted PRH and that inhibition of TGFβ signalling blocks the effects of platelets on these cells. Moreover, TGFβ induces changes characteristic of EMT including decreased E-Cadherin expression and increased Snail expression. We show that in prostate cells PRH regulates multiple genes involved in EMT and TGFβ signalling. However, both platelets and TGFβ increase PRH phosphorylation. In addition, TGFβ increases binding of its effector pSMAD3 to the PRH/HHEX promoter and downregulates PRH protein and mRNA levels. Thus, TGFβ signalling downregulates PRH activity by multiple mechanisms and induces an EMT that facilitates extravasation and sensitises cells to TGFβ.
Identifiers
What OpenQuestion holds
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.