ArticleMolecular biology of the cell2012
Matrix compliance regulates Rac1b localization, NADPH oxidase assembly, and epithelial-mesenchymal transition.
Article in Molecular biology of the cell, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers.
What it found
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Who cites it
71 citing papers in PubMed, 110 citations in OpenAlex.
- A Novel Pharmacologic Activity of Ketorolac for Therapeutic Benefit in Ovarian Cancer Patients.Clinical cancer research : an official journal of the American Association for Cancer Research · 2015Trial
- Tunable Enhancement of T Cell Expansion Through Modulation of Stiffness and Adhesion Receptor Engagement in an Engineered Hydrogel Platform.Advanced materials (Deerfield Beach, Fla.) · 2026Article
- Substrate stiffness regulates triple-negative breast cancer signaling through CXCR4 receptor dynamics.Scientific reports · 2025Article
- Effects of NaCell biochemistry and biophysics · 2025Review
- Matrix metalloproteinase-driven epithelial-mesenchymal transition: implications in health and disease.Journal of translational medicine · 2025Review
- Alternative Splicing at the Crossroad of Inflammatory Bowel Diseases and Colitis-Associated Colon Cancer.Cancers · 2025Review
- The Roles of RAC1 and RAC1B in Colorectal Cancer and Their Potential Contribution to Cetuximab Resistance.Cancers · 2024Review
- Matrix stiffening promotes perinuclear clustering of mitochondria.Molecular biology of the cell · 2024Article
- Involvement of Matricellular Proteins in Cellular Senescence: Potential Therapeutic Targets for Age-Related Diseases.International journal of molecular sciences · 2024Review
- Cancer cell response to extrinsic and intrinsic mechanical cue: opportunities for tumor apoptosis strategies.Regenerative biomaterials · 2024Review
- Targeted splicing therapy: new strategies for colorectal cancer.Frontiers in oncology · 2023Review
- ECM stiffness modulates the proliferation but not the motility of primary corneal keratocytes in response to PDGF-BB.Experimental eye research · 2022Article
- Biophysics Role and Biomimetic Culture Systems of ECM Stiffness in Cancer EMT.Global challenges (Hoboken, NJ) · 2022Review
- Ultrasound-Induced Mechanical Compaction in Acoustically Responsive Scaffolds Promotes Spatiotemporally Modulated Signaling in Triple Negative Breast Cancer.Advanced healthcare materials · 2022Article
- Pro-Inflammatory Cytokines Trigger the Overexpression of Tumour-Related Splice Variant RAC1B in Polarized Colorectal Cells.Cancers · 2022Article
- Matrix mechanics regulates epithelial defence against cancer by tuning dynamic localization of filamin.Nature communications · 2022Article
- Bioelectric Dysregulation in Cancer Initiation, Promotion, and Progression.Frontiers in oncology · 2022Review
- Substrate stiffness effect on molecular crosstalk of epithelial-mesenchymal transition mediators of human glioblastoma cells.Frontiers in oncology · 2022Article
- Substratum stiffness signals through integrin-linked kinase and β1-integrin to regulate midbody proteins and abscission during EMT.Molecular biology of the cell · 2021Article
- Mechanoresponsive metabolism in cancer cell migration and metastasis.Cell metabolism · 2021Review
11 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Epithelial-mesenchymal transition (EMT) is a form of epithelial plasticity implicated in fibrosis and tumor metastasis. Here we show that the mechanical rigidity of the microenvironment plays a pivotal role in the promotion of EMT by controlling the subcellular localization and downstream signaling of Rac GTPases. Soft substrata, with compliances comparable to that of normal mammary tissue, are protective against EMT, whereas stiffer substrata, with compliances characteristic of breast tumors, promote EMT. Rac1b, a highly activated splice variant of Rac1 found in tumors, localizes to the plasma membrane in cells cultured on stiff substrata or in collagen-rich regions of human breast tumors. At the membrane, Rac1b forms a complex with NADPH oxidase and promotes the production of reactive oxygen species, expression of Snail, and activation of the EMT program. In contrast, soft microenvironments inhibit the membrane localization of Rac1b and subsequent redox changes. These results reveal a novel mechanotransduction pathway in the regulation of epithelial plasticity via EMT.
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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.