ArticleCellular and molecular life sciences : CMLS2020
HAS3-induced extracellular vesicles from melanoma cells stimulate IHH mediated c-Myc upregulation via the hedgehog signaling pathway in target cells.
Article in Cellular and molecular life sciences : CMLS, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 47 citations in OpenAlex.
- Hyaluronic Acid Decoration Facilitates CD44-Mediated Targeting and Alters Protein Corona Formation of Extracellular Vesicles.Journal of extracellular vesicles · 2026Article
- Mechanical regulation of extracellular vesicle activity during tumour progression.Nature biomedical engineering · 2025Review
- Potential of CLSPN as a therapeutic target in melanoma: a key player in melanoma progression and tumor microenvironment.Journal of translational medicine · 2025Article
- Review
- The involvement of RIPK4 in TNF-α-stimulated IL-6 and IL-8 production by melanoma cells.Journal of cancer research and clinical oncology · 2024Article
- Hitting the target: cell signaling pathways modulation by extracellular vesicles.Extracellular vesicles and circulating nucleic acids · 2024Review
- A multi-omics analysis reveals CLSPN is associated with prognosis, immune microenvironment and drug resistance in cancers.Biological procedures online · 2023Article
- Role of PAX2 in breast cancer verified by bioinformatics analysis andAnnals of translational medicine · 2023Article
- Tumor-derived extracellular vesicles as messengers of natural products in cancer treatment.Theranostics · 2022Review
- The Effects of Hedgehog Signaling Pathway on the Proliferation and Apoptosis of Melanoma Cells.Journal of oncology · 2022Article
- MCF10CA Breast Cancer Cells Utilize Hyaluronan-Coated EV-Rich Trails for Coordinated Migration.Frontiers in oncology · 2022Article
- LncRNA BASP1-AS1 interacts with YBX1 to regulate Notch transcription and drives the malignancy of melanoma.Cancer science · 2021Article
- Glycocalyx Curving the Membrane: Forces Emerging from the Cell Exterior.Annual review of cell and developmental biology · 2021Review
- Diverse plasma membrane protrusions act as platforms for extracellular vesicle shedding.Journal of extracellular vesicles · 2021Review
- Inflammation, Extracellular Matrix Remodeling, and Proteostasis in Tumor Microenvironment.International journal of molecular sciences · 2021Review
- Tumor microenvironment immune-related lncRNA signature for patients with melanoma.Annals of translational medicine · 2021Article
- Bacterial Membrane Vesicles in Pneumonia: From Mediators of Virulence to Innovative Vaccine Candidates.International journal of molecular sciences · 2021Review
- Ciliary extracellular vesicles are distinct from the cytosolic extracellular vesicles.Journal of extracellular vesicles · 2021Article
- Uncovering the Depths of the Human Proteome: Antibody-based Technologies for Ultrasensitive Multiplexed Protein Detection and Quantification.Molecular & cellular proteomics : MCP · 2021Review
- The Impact of Hyaluronan on Tumor Progression in Cutaneous Melanoma.Frontiers in oncology · 2021Review
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Authors and funding
13 authors at 2 institutions in 1 country.
Funding
Abstract
Intercellular communication is fundamental to the survival and maintenance of all multicellular systems, whereas dysregulation of communication pathways can drive cancer progression. Extracellular vesicles (EVs) are mediators of cell-to-cell communication that regulate a variety of cellular processes involved in tumor progression. Overexpression of a specific plasma membrane enzyme, hyaluronan synthase 3 (HAS3), is one of the factors that can induce EV shedding. HAS3, and particularly its product hyaluronan (HA), are carried by EVs and are known to be associated with the tumorigenic properties of cancer cells. To elucidate the specific effects of cancerous, HAS3-induced EVs on target cells, normal human keratinocytes and melanoma cells were treated with EVs derived from GFP-HAS3 expressing metastatic melanoma cells. We found that the HA receptor CD44 participated in the regulation of EV binding to target cells. Furthermore, GFP-HAS3-positive EVs induced HA secretion, proliferation and invasion of target cells. Our results suggest that HAS3-EVs contains increased quantities of IHH, which activates the target cell hedgehog signaling cascade and leads to the activation of c-Myc and regulation of claspin expression. This signaling of IHH in HAS3-EVs resulted in increased cell proliferation. Claspin immunostaining correlated with HA content in human cutaneous melanocytic lesions, supporting our in vitro findings and suggesting a reciprocal regulation between claspin expression and HA synthesis. This study shows for the first time that EVs originating from HAS3 overexpressing cells carry mitogenic signals that induce proliferation and epithelial-to-mesenchymal transition in target cells. The study also identifies a novel feedback regulation between the hedgehog signaling pathway and HA metabolism in melanoma, mediated by EVs carrying HA and IHH.
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Registered trials
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