ArticleScientific reports2018
Matrilysin/MMP-7 Cleavage of Perlecan/HSPG2 Complexed with Semaphorin 3A Supports FAK-Mediated Stromal Invasion by Prostate Cancer Cells.
Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 36 citations in OpenAlex.
- Proteoglycans as Molecular Regulators of Bone Metastasis: Extracellular Matrix Remodeling, Tumor-Bone Crosstalk, Dormancy, and Therapeutic Opportunities.Biomolecules · 2026Review
- A guide to the types, structures, and multifaceted functions of matrix metalloproteinases in cancer.The FEBS journal · 2026Review
- Proteoglycans in Prostate Cancer Progression and Therapy Resistance.Medicina (Kaunas, Lithuania) · 2025Review
- Ageing-Related Changes in Ultrastructural Bone Matrix Composition and Osteocyte Mechanosensitivity.Current osteoporosis reports · 2025Review
- A novel bone metastasis-related gene signature for predicting prognosis, anti-androgen resistance, and drug choice in prostate cancer.Journal of bone oncology · 2025Article
- Distinct role of perlecan in mesenchymal tissue regeneration via genetic and epigenetic modification.Chemical engineering journal (Lausanne, Switzerland : 1996) · 2025Article
- Comprehensive pan-cancer analysis of HSPG2 as a marker for prognosis.BMC medical genomics · 2025Article
- Diverse and multifunctional roles for perlecan (JOR spine · 2024Review
- Extracellular cancer‑associated fibroblasts: A novel subgroup in the cervical cancer microenvironment that exhibits tumor‑promoting roles and prognosis biomarker functions.Oncology letters · 2024Article
- The genomic and evolutionary landscapes of anaplastic thyroid carcinoma.Cell reports · 2024Article
- The Potential of Extracellular Matrix- and Integrin Adhesion Complex-Related Molecules for Prostate Cancer Biomarker Discovery.Biomedicines · 2023Review
- Advances in landscape and related therapeutic targets of the prostate tumor microenvironment.Acta biochimica et biophysica Sinica · 2023Review
- Important Cells and Factors from Tumor Microenvironment Participated in Perineural Invasion.Cancers · 2023Review
- Review
- Article
- Substituted Syndecan-2-Derived Mimetic Peptides Show Improved Antitumor Activity over the Parent Syndecan-2-Derived Peptide.International journal of molecular sciences · 2022Article
- Article
- Cleavage of the Perlecan-Semaphorin 3A-Plexin A1-Neuropilin-1 (PSPN) Complex by Matrix Metalloproteinase 7/Matrilysin Triggers Prostate Cancer Cell Dyscohesion and Migration.International journal of molecular sciences · 2021Article
- Proteoglycan-driven Autophagy: A Nutrient-independent Mechanism to Control Intracellular Catabolism.The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society · 2020Review
- Roles of Proteoglycans and Glycosaminoglycans in Cancer Development and Progression.International journal of molecular sciences · 2020Review
Corrections and comments
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Authors and funding
8 authors at 5 institutions in 1 country.
Funding
Abstract
Interrupting the interplay between cancer cells and extracellular matrix (ECM) is a strategy to halt tumor progression and stromal invasion. Perlecan/heparan sulfate proteoglycan 2 (HSPG2) is an extracellular proteoglycan that orchestrates tumor angiogenesis, proliferation, differentiation and invasion. Metastatic prostate cancer (PCa) cells degrade perlecan-rich tissue borders to reach bone, including the basement membrane, vasculature, reactive stromal matrix and bone marrow. Domain IV-3, perlecan's last 7 immunoglobulin repeats, mimics native proteoglycan by promoting tumoroid formation. This is reversed by matrilysin/matrix metalloproteinase-7 (MMP-7) cleavage to favor cell dispersion and tumoroid dyscohesion. Both perlecan and Domain IV-3 induced a strong focal adhesion kinase (FAK) dephosphorylation/deactivation. MMP-7 cleavage of perlecan reversed this, with FAK in dispersed tumoroids becoming phosphorylated/activated with metastatic phenotype. We demonstrated Domain IV-3 interacts with the axon guidance protein semaphorin 3A (Sema3A) on PCa cells to deactivate pro-metastatic FAK. Sema3A antibody mimicked the Domain IV-3 clustering activity. Direct binding experiments showed Domain IV-3 binds Sema3A. Knockdown of Sema3A prevented Domain IV-3-induced tumoroid formation and Sema3A was sensitive to MMP-7 proteolysis. The perlecan-Sema3A complex abrogates FAK activity and stabilizes PCa cell interactions. MMP-7 expressing cells destroy the complex to initiate metastasis, destroy perlecan-rich borders, and favor invasion and progression to lethal bone disease.
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