ArticleProceedings of the National Academy of Sciences of the United States of America2019
Dynamically stiffened matrix promotes malignant transformation of mammary epithelial cells via collective mechanical signaling.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 88 papers.
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Who cites it
88 citing papers in PubMed.
- Mechanical Intelligence in Bone Regeneration: Bridging Material and Cellular Memory for Enhanced Healing.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Integrin-Piezo1 Axis Drives ECM Remodeling and Invasion of 3D Breast Epithelium.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Interaction between m6A and YAP1 mechanotransduction pathways is essential for mechanical memory and matrix remodeling in pancreatic cancer.International journal of biological sciences · 2026Article
- Extracellular matrix physical properties regulate cancer cell morphological transitions in 3D hydrogel microtissues.Acta biomaterialia · 2026Article
- Extracellular matrix stiffness conditions glioblastoma cells for long-term migration: Mechanical memory as a driver of invasion and recurrence in glioblastoma.Neuro-oncology · 2026Review
- The RNA-binding protein RNP1A is essential and interacts with contractility kit proteins to facilitate cell mechanics.Journal of cell science · 2026Article
- Article
- Tumor-Tissue Boundaries as Instructive Interfaces in Breast Cancer Cell Invasion.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Adaptation to Volumetric Compression Drives an Apoptosis-Resistant and Invasive Phenotype in Liver Cancer.Cancer research · 2025Article
- Targeting breast tumor extracellular matrix and stroma utilizing nanoparticles.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2025Review
- Matrix Stiffness Regulates TGFβ1-Induced αSMA Expression via a G9a-LATS-YAP Signaling Cascade.FASEB bioAdvances · 2025Article
- Increased matrix stiffness promotes fibrogenesis of hepatic stellate cells through AP-1-induced chromatin priming.Communications biology · 2025Article
- The balance between N1 and N2 neutrophils implications for breast cancer immunotherapy: a narrative review.Annals of medicine and surgery (2012) · 2025Review
- Full-thickness cervix reconstruction via collagen scaffolds in rabbits.Bioactive materials · 2025Article
- Review
- Cellular mechanical memory: a potential tool for mesenchymal stem cell-based therapy.Stem cell research & therapy · 2025Review
- Insights into the mechanisms, regulation, and therapeutic implications of extracellular matrix stiffness in cancer.Bioengineering & translational medicine · 2025Review
- Review
- Genetic variation drives cancer cell adaptation to ECM stiffness.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Tissue Mechanics and Hedgehog Signaling Crosstalk as a Key Epithelial-Stromal Interplay in Cancer Development.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
28 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors.
Funding
Abstract
Breast cancer development is associated with increasing tissue stiffness over years. To more accurately mimic the onset of gradual matrix stiffening, which is not feasible with conventional static hydrogels, mammary epithelial cells (MECs) were cultured on methacrylated hyaluronic acid hydrogels whose stiffness can be dynamically modulated from "normal" (<150 Pascals) to "malignant" (>3,000 Pascals) via two-stage polymerization. MECs form and remain as spheroids, but begin to lose epithelial characteristics and gain mesenchymal morphology upon matrix stiffening. However, both the degree of matrix stiffening and culture time before stiffening play important roles in regulating this conversion as, in both cases, a subset of mammary spheroids remained insensitive to local matrix stiffness. This conversion depended neither on colony size nor cell density, and MECs did not exhibit "memory" of prior niche when serially cultured through cycles of compliant and stiff matrices. Instead, the transcription factor Twist1, transforming growth factor β (TGFβ), and YAP activation appeared to modulate stiffness-mediated signaling; when stiffness-mediated signals were blocked, collective MEC phenotypes were reduced in favor of single MECs migrating away from spheroids. These data indicate a more complex interplay of time-dependent stiffness signaling, spheroid structure, and soluble cues that regulates MEC plasticity than suggested by previous models.
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