ArticleCancers2021
A Theoretical Approach to Coupling the Epithelial-Mesenchymal Transition (EMT) to Extracellular Matrix (ECM) Stiffness via LOXL2.
Article in Cancers, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 62 citations in OpenAlex.
- Biofabrication and artificial intelligence strategies for investigating solid- and fluid-pressure mechanobiology in pancreatic ductal adenocarcinoma.Cancer metastasis reviews · 2026Review
- Targeting Wnt3a and Loxl2 Synergistically Induces Ferroptosis in Liver Cancer Stem Cells and Suppresses Tumorigenesis.Cancer science · 2026Article
- Inflammatory bowel disease and extracellular matrix: when victim becomes double agent.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Review
- Regulatory network and spatial modeling reveal cooperative mechanisms of resistance and immune escape in ER+ breast cancer.BMC cancer · 2026Article
- The mechano-immunological barrier in fibrosis-associated lung cancer: targeting matrix stiffness and the Piezo1 axis for microenvironment normalization.Frontiers in pharmacology · 2026Review
- Research progress on tumor extracellular matrix stiffness and immunosuppression.Frontiers in immunology · 2026Review
- TAGLN: a stiffness-driven prognostic biomarker for metastatic colorectal cancer.Cancer cell international · 2025Article
- Regulatory network and spatial modeling reveal cooperative mechanisms of resistance and immune escape in ER+ breast cancer.bioRxiv : the preprint server for biology · 2025Article
- Matrix: a complex amalgam of structures and functions in tumor microenvironment.FEBS open bio · 2025Review
- An integrative phenotype-structured partial differential equation model for the population dynamics of epithelial-mesenchymal transition.NPJ systems biology and applications · 2025Article
- Viscosity regulates cell spreading and cell-extracellular matrix interactions.The FEBS journal · 2025Article
- Mechanistic insights into epithelial-mesenchymal transition mediated cisplatin resistance in ovarian cancer.Scientific reports · 2025Article
- Deciphering molecular pathways driving cancer invasion and metastasis: advances and therapeutic prospects.Frontiers in oncology · 2025Review
- Pre-metastatic niche: formation, characteristics and therapeutic implication.Signal transduction and targeted therapy · 2024Review
- Impact of Respiratory Dust on Health: A Comparison Based on the Toxicity of PM2.5, Silica, and Nanosilica.International journal of molecular sciences · 2024Review
- Mammary tissue-derived extracellular matrix hydrogels reveal the role of irradiation in driving a pro-tumor and immunosuppressive microenvironment.Biomaterials · 2024Article
- Cancer spreading patterns based on epithelial-mesenchymal plasticity.Frontiers in cell and developmental biology · 2024Article
- Impaired angiogenesis in ageing: the central role of the extracellular matrix.Journal of translational medicine · 2023Review
- Extracellular matrix remodeling in tumor progression and immune escape: from mechanisms to treatments.Molecular cancer · 2023Review
- Pin1/YAP pathway mediates matrix stiffness-induced epithelial-mesenchymal transition driving cervical cancer metastasis via a non-Hippo mechanism.Bioengineering & translational medicine · 2023Article
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 2 countries.
Funding
Abstract
The epithelial-mesenchymal transition (EMT) plays a critical role in cancer progression, being responsible in many cases for the onset of the metastatic cascade and being integral in the ability of cells to resist drug treatment. Most studies of EMT focus on its induction via chemical signals such as TGF-β or Notch ligands, but it has become increasingly clear that biomechanical features of the microenvironment such as extracellular matrix (ECM) stiffness can be equally important. Here, we introduce a coupled feedback loop connecting stiffness to the EMT transcription factor ZEB1, which acts via increasing the secretion of LOXL2 that leads to increased cross-linking of collagen fibers in the ECM. This increased cross-linking can effectively increase ECM stiffness and increase ZEB1 levels, thus setting a positive feedback loop between ZEB1 and ECM stiffness. To investigate the impact of this non-cell-autonomous effect, we introduce a computational approach capable of connecting LOXL2 concentration to increased stiffness and thereby to higher ZEB1 levels. Our results indicate that this positive feedback loop, once activated, can effectively lock the cells in a mesenchymal state. The spatial-temporal heterogeneity of the LOXL2 concentration and thus the mechanical stiffness also has direct implications for migrating cells that attempt to escape the primary tumor.
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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.