ArticlePloS one2019
Recombinant human PRG4 (rhPRG4) suppresses breast cancer cell invasion by inhibiting TGFβ-Hyaluronan-CD44 signalling pathway.
Article in PloS one, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 36 citations in OpenAlex.
- Unveiling the Mysteries of CLEC3B: Physiological Roles, Pathological Impacts, and Research Gaps.Cells · 2026Review
- YAP/TAZ inhibition refines TGF-β signaling to prevent laryngeal fibrosis.bioRxiv : the preprint server for biology · 2026Article
- Combinatorial Effects of 5-Fluorouracil and Menadione on Wnt/β-Catenin Pathway in Human Colorectal Cancer Cells.Applied biochemistry and biotechnology · 2025Article
- Organoids in breast cancer translational research: intersection of technologies.Translational breast cancer research : a journal focusing on translational research in breast cancer · 2025Review
- Informed by Cancer Stem Cells of Solid Tumors: Advances in Treatments Targeting Tumor-Promoting Factors and Pathways.International journal of molecular sciences · 2024Review
- Interrogations of single-cell RNA splicing landscapes with SCASL define new cell identities with physiological relevance.Nature communications · 2024Article
- Sumoylated SnoN interacts with HDAC1 and p300/CBP to regulate EMT-associated phenotypes in mammary organoids.Cell death & disease · 2023Article
- Quantifiable peptide library bridges the gap for proteomics based biomarker discovery and validation on breast cancer.Scientific reports · 2023Article
- Redlining-associated methylation in breast tumors: the impact of contemporary structural racism on the tumor epigenome.Frontiers in oncology · 2023Article
- Tumor molecular differences associated with outcome disparities of Black patients with head and neck cancer.Head & neck · 2022Article
- Proteoglycans in Cancer: Friends or Enemies? A Special Focus on Hepatocellular Carcinoma.Cancers · 2022Review
- Mechanisms of Cell Adhesion Molecules in Endocrine-Related Cancers: A Concise Outlook.Frontiers in endocrinology · 2022Review
- CD44 Glycosylation as a Therapeutic Target in Oncology.Frontiers in oncology · 2022Review
- Noncovalent hyaluronan crosslinking by TSG-6: Modulation by heparin, heparan sulfate, and PRG4.Frontiers in molecular biosciences · 2022Article
- Proteoglycan-4 predicts good prognosis in patients with hepatocellular carcinoma receiving transcatheter arterial chemoembolization and inhibits cancer cell migrationFrontiers in oncology · 2022Article
- TGF-B1-over-expressed adipose stem cells-derived secretome exhibits CD44 suppressor and anti-cancer properties via antagonistic effects against SMAD4 in breast cancer cells.American journal of stem cells · 2022Article
- Proteoglycan 4 (PRG4) expression and function in dry eye associated inflammation.Experimental eye research · 2021Article
- Proteoglycan 4 Reduces Neuroinflammation and Protects the Blood-Brain Barrier after Traumatic Brain Injury.Journal of neurotrauma · 2021Article
- Prognostic Effect of Inflammatory Genes on Stage I-III Colorectal Cancer-Integrative Analysis of TCGA Data.Cancers · 2021Article
- Proteoglycan-4 is correlated with longer survival in HCC patients and enhances sorafenib and regorafenib effectiveness via CD44 in vitro.Cell death & disease · 2020Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Metastasis is the major cause of cancer-related morbidity and mortality. The ability of cancer cells to become invasive and migratory contribute significantly to metastatic growth, which necessitates the identification of novel anti-migratory and anti-invasive therapeutic approaches. Proteoglycan 4 (PRG4), a mucin-like glycoprotein, contributes to joint synovial homeostasis through its friction-reducing and anti-adhesive properties. Adhesion to surrounding extracellular matrix (ECM) components is critical for cancer cells to invade the ECM and eventually become metastatic, raising the question whether PRG4 has an anti-invasive effect on cancer cells. Here, we report that a full-length recombinant human PRG4 (rhPRG4) suppresses the ability of the secreted protein transforming growth factor beta (TGFβ) to induce phenotypic disruption of three-dimensional human breast cancer cell-derived organoids by reducing ligand-induced cell invasion. In mechanistic studies, we find that rhPRG4 suppresses TGFβ-induced invasiveness of cancer cells by inhibiting the downstream hyaluronan (HA)-cell surface cluster of differentiation 44 (CD44) signalling axis. Furthermore, we find that rhPRG4 represses TGFβ-dependent increase in the protein abundance of CD44 and of the enzyme HAS2, which is involved in HA biosynthesis. It is widely accepted that TGFβ has both tumor suppressing and tumor promoting roles in cancer. The novel finding that rhPRG4 opposes HAS2 and CD44 induction by TGFβ has implications for downregulating the tumor promoting roles, while maintaining the tumor suppressive aspects of TGFβ actions. Finally, these findings point to rhPRG4's potential clinical utility as a therapeutic treatment for invasive and metastatic breast cancer.
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