ArticleDevelopmental cell2020
Matrix Rigidity Controls Epithelial-Mesenchymal Plasticity and Tumor Metastasis via a Mechanoresponsive EPHA2/LYN Complex.
Article in Developmental cell, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 172 papers.
What it found
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Who cites it
172 citing papers in PubMed, 240 citations in OpenAlex.
- Myofibroblastic CAF and Malignant Ductal Cell Crosstalk Drives Epithelial-Mesenchymal Transition and Progression in Pancreatic Ductal Adenocarcinoma via THBS2-SDC/Integrin Axes.International journal of molecular sciences · 2026Article
- Matrix Stiffness Drives Aggressive Phenotype in Tongue Squamous Cell Carcinoma via Mechanotransduction-Stromal Signalling.International dental journal · 2026Article
- Matricellular Proteins in Bladder Cancer: Context-Dependent Roles in Tumor Promotion and Suppression.International journal of molecular sciences · 2026Review
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- Targeting mechanosensitive EphA2 phase separation to alleviate arterial stiffening.Bioactive materials · 2026Article
- Nuclear Mechanotransduction Across the Metastatic Cascade: Decoding Spatiotemporal Heterogeneity in Cancer Dissemination.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Stiffness-related stress granules promote the metastasis of early-stage oral squamous cell carcinoma via anoikis resistance.Cellular oncology (Dordrecht, Netherlands) · 2026Article
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- Epithelial-to-mesenchymal transition as a central driver of tumor cell plasticity.Nature cancer · 2026Review
- The role and mechanism by which micropeptide WHPP promote refractory wound healing.Journal of translational medicine · 2026Article
- Extracellular matrix rigidity controls breast cancer metastasis via TYK2-mediated mechanotransduction.Nature communications · 2026Article
- Notch1 O-GlcNAcylation drives tumor stemness and mechanoadaptation to a stiff microenvironment and promotes chordoma recurrence.The Journal of clinical investigation · 2026Article
- Fluid shear stress activates a targetable mechano-metastatic cascade to promote medulloblastoma metastasis.Nature biomedical engineering · 2026Article
- Targeting EphA2 under DNA damage causes mitotic bypass via p21 induction.The Journal of biological chemistry · 2026Article
- A systems approach identifies MERTK as a therapeutic vulnerability in ZFTA-RELA-driven ependymomas.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Research Progress on the Biological Function, Disease-Driving Mechanism and Clinical Targeting Strategies of G3BP2.Molecules (Basel, Switzerland) · 2026Review
- PCSK5M452I Is a Recessive Hypomorph Exclusive to MCF10DCIS.com Cells.Molecular cancer research : MCR · 2026Article
- Targeting Matrix Stiffness and Mechanotransduction in Breast Cancer: Implications for Emerging Therapies.International journal of molecular sciences · 2026Review
- Features of the spatial organization and qualitative composition of the collagen matrix in prostate cancer.Journal of molecular histology · 2026Article
- Identification, functional insights and therapeutic targeting of EMT tumour states.Nature reviews. Cancer · 2026Review
112 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
Mechanical cues from the extracellular matrix (ECM) regulate various cellular processes via distinct mechanotransduction pathways. In breast cancer, increased ECM stiffness promotes epithelial-to-mesenchymal transition (EMT), cell invasion, and metastasis. Here, we identify a mechanosensitive EPHA2/LYN protein complex regulating EMT and metastasis in response to increasing ECM stiffness during tumor progression. High ECM stiffness leads to ligand-independent phosphorylation of ephrin receptor EPHA2, which recruits and activates the LYN kinase. LYN phosphorylates the EMT transcription factor TWIST1 to release TWIST1 from its cytoplasmic anchor G3BP2 to enter the nucleus, thus triggering EMT and invasion. Genetic and pharmacological inhibition of this pathway prevents breast tumor invasion and metastasis in vivo. In human breast cancer samples, activation of this pathway correlates with collagen fiber alignment, a marker of increasing ECM stiffness. Our findings reveal an EPHA2/LYN/TWIST1 mechanotransduction pathway that responds to mechanical signals from the tumor microenvironment to drive EMT, invasion, and metastasis.
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Registered trials
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.