ArticleNature materials2021
Basement membrane stiffness determines metastases formation.
Article in Nature materials, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 105 papers.
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Who cites it
105 citing papers in PubMed, 178 citations in OpenAlex.
- Targeting the C/EBPβ-PRAME-EZH2 complex modulates the Netrin-4/AKT axis to inhibit renal cancer tumorigenesis and metastasis.Cell death and differentiation · 2026Article
- Identification of colorectal cancer molecular subtypes and prognostic features based on basement membrane-related genes.Journal of applied genetics · 2026Article
- Curcumol Inhibits the Laminin-Facilitated Malignant Progression in Small-Cell Lung Cancer via Disrupting Laminin-Integrin β1 Interaction.Phytotherapy research : PTR · 2026Article
- Proteolytic remodelling of the extracellular matrix by pericytes.The FEBS journal · 2026Review
- Basement membrane related genes in lung adenocarcinoma prognostic risk model based on single cell and bulk RNA sequencing and tumor microenvironment modulation.Discover oncology · 2026Article
- EGFL6 predicts unfavorable prognosis and serves as a potential indicator in esophageal carcinoma.Discover oncology · 2026Article
- Cancer Neoaxonogenesis: Mechanisms and Factors Involved in the Recruitment of Peripheral Nerves by Cancer Tissue.International journal of molecular sciences · 2026Review
- Identification of Basement Membrane-Related Biomarkers in the Progression of Cutaneous Squamous Cell Carcinoma.International journal of molecular sciences · 2026Article
- Sulforaphane as a Multi-Scale Mechano-Modulator in Cancer: An Integrative Perspective.Biology · 2026Article
- Cancer cells metastasize in several types of cancer via two distinct routes, probably based on mechanical signals.Frontiers in cell and developmental biology · 2026Review
- Article
- Integrin-Piezo1 Axis Drives ECM Remodeling and Invasion of 3D Breast Epithelium.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Untangling the fusion of spatial omics and mechanobiology.Progress in biomedical engineering (Bristol, England) · 2025Review
- The Role of Extracellular Proteases and Extracellular Matrix Remodeling in the Pre-Metastatic Niche.Biomolecules · 2025Review
- Loss of the extracellular protease ADAMTS1 reveals an antitumorigenic program involving the action of NIDOGEN-1 on macrophage polarization.Oncoimmunology · 2025Article
- Basement membrane structure and function: Relating biology to mechanics.Matrix biology : journal of the International Society for Matrix Biology · 2025Review
- Enhanced nanoparticle delivery across vascular basement membranes of tumours using nitric oxide.Nature biomedical engineering · 2025Article
- Cryo-EM reveals molecular mechanisms underlying the inhibitory effect of netrin-4 on laminin matrix formation.Nature communications · 2025Article
- ECM formation and degradation during fibrosis, repair, and regeneration.npj metabolic health and disease · 2025Review
- Shaping epithelial tissues by stem cell mechanics in development and cancer.Nature reviews. Molecular cell biology · 2025Review
45 more citing papers are in PubMed but not listed here.
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Authors and funding
31 authors at 11 institutions in 6 countries.
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Abstract
The basement membrane (BM) is a special type of extracellular matrix and presents the major barrier cancer cells have to overcome multiple times to form metastases. Here we show that BM stiffness is a major determinant of metastases formation in several tissues and identify netrin-4 (Net4) as a key regulator of BM stiffness. Mechanistically, our biophysical and functional analyses in combination with mathematical simulations show that Net4 softens the mechanical properties of native BMs by opening laminin node complexes, decreasing cancer cell potential to transmigrate this barrier despite creating bigger pores. Our results therefore reveal that BM stiffness is dominant over pore size, and that the mechanical properties of 'normal' BMs determine metastases formation and patient survival independent of cancer-mediated alterations. Thus, identifying individual Net4 protein levels within native BMs in major metastatic organs may have the potential to define patient survival even before tumour formation. The ratio of Net4 to laminin molecules determines BM stiffness, such that the more Net4, the softer the BM, thereby decreasing cancer cell invasion activity.
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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.