ArticleThe Biochemical journal2012
Platelet-derived growth factor-C (PDGF-C) activation by serine proteases: implications for breast cancer progression.
Article in The Biochemical journal, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 50 citations in OpenAlex.
- Platelet-derived growth factor-C (PDGF-C) induces anti-apoptotic effects on macrophages through Akt and Bad phosphorylation.The Journal of biological chemistry · 2014Trial
- Clinical utilities of platelet-derived growth factor signaling in breast cancer.Pharmacological research · 2026Review
- The Role of Blood-Brain Barrier Disruption in Epilepsy: Mechanisms and Consequences.Neurology international · 2025Review
- The SUMO Family: Mechanisms and Implications in Thyroid Cancer Pathogenesis and Therapy.Biomedicines · 2024Review
- Age-associated microenvironmental changes highlight the role of PDGF-C in ERNature cancer · 2023Article
- Imatinib facilitates gemcitabine sensitivity by targeting epigenetically activated PDGFC signaling in pancreatic cancer.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Article
- The production of recombinant platelet-derived growth factor D using the second generation modified vaccinia Ankara viral system.Protein science : a publication of the Protein Society · 2022Article
- Insufficiency of hepatocyte growth factor activator inhibitor-1 confers lymphatic invasion of tongue carcinoma cells.Cancer science · 2022Article
- Glycosylation at Asn254 Is Required for the Activation of the PDGF-C Protein.Frontiers in molecular biosciences · 2021Article
- CD146, from a melanoma cell adhesion molecule to a signaling receptor.Signal transduction and targeted therapy · 2020Review
- Cell surface-anchored serine proteases in cancer progression and metastasis.Cancer metastasis reviews · 2019Review
- An oncogenic activity of PDGF-C and its splice variant in human breast cancer.Growth factors (Chur, Switzerland) · 2019Article
- PHD3 Acts as Tumor Suppressor in Mouse Osteosarcoma and Influences Tumor Vascularization via PDGF-C Signaling.Cancers · 2018Article
- PDGF/PDGFR axis in the neural systems.Molecular aspects of medicine · 2018Review
- The Phenotypic Effects of Exosomes Secreted from Distinct Cellular Sources: a Comparative Study Based on miRNA Composition.The AAPS journal · 2018Article
- Pharmacological targeting of the PDGF-CC signaling pathway for blood-brain barrier restoration in neurological disorders.Pharmacology & therapeutics · 2016Review
- Matriptase activation and shedding through PDGF-D-mediated extracellular acidosis.American journal of physiology. Cell physiology · 2016Article
- MAPK1/ERK2 as novel target genes for pain in head and neck cancer patients.BMC genetics · 2016Article
- Changes in neutrophil/lymphocyte and platelet/lymphocyte ratios after chemotherapy correlate with chemotherapy response and prediction of prognosis in patients with unresectable gastric cancer.Oncology letters · 2015Article
- Post-transcriptional up-regulation of PDGF-C by HuR in advanced and stressed breast cancer.International journal of molecular sciences · 2014Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
The PDGF (platelet-derived growth factor) family members are potent mitogens for cells of mesenchymal origin and serve as important regulators of cell migration, survival, apoptosis and transformation. Tumour-derived PDGF ligands are thought to function in both autocrine and paracrine manners, activating receptors on tumour and surrounding stromal cells. PDGF-C and -D are secreted as latent dimers, unlike PDGF-A and -B. Cleavage of the CUB domain from the PDGF-C and -D dimers is required for their biological activity. At present, little is known about the proteolytic processing of PDGF-C, the rate-limiting step in the regulation of PDGF-C activity. In the present study we show that the breast carcinoma cell line MCF7, engineered to overexpress PDGF-C, produces proteases capable of cleaving PDGF-C to its active form. Increased PDGF-C expression enhances cell proliferation, anchorage-independent cell growth and tumour cell motility by autocrine signalling. In addition, MCF7-produced PDGF-C induces fibroblast cell migration in a paracrine manner. Interestingly, PDGF-C enhances tumour cell invasion in the presence of fibroblasts, suggesting a role for tumour-derived PDGF-C in tumour-stromal interactions. In the present study, we identify tPA (tissue plasminogen activator) and matriptase as major proteases for processing of PDGF-C in MCF7 cells. In in vitro studies, we also show that uPA (urokinase-type plasminogen activator) is able to process PDGF-C. Furthermore, by site-directed mutagenesis, we identify the cleavage site for these proteases in PDGF-C. Lastly, we provide evidence suggesting a two-step proteolytic processing of PDGF-C involving creation of a hemidimer, followed by GFD-D (growth factor domain dimer) generation.
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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.