ArticleCancer research2014
Force engages vinculin and promotes tumor progression by enhancing PI3K activation of phosphatidylinositol (3,4,5)-triphosphate.
Article in Cancer research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 128 papers.
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Who cites it
128 citing papers in PubMed.
- Forces that shape the transcriptome: Linking cellular mechanosensing to mRNA splicing.The Journal of biological chemistry · 2026Review
- Metabolic permissiveness: how tissue context shapes cancer.Genes & development · 2026Review
- Modulation of the Mechanosensory Matrisome by Serotonergic Signaling.Results and problems in cell differentiation · 2026Review
- Unraveling the role of the WIPF1/ACTN4 complex in podosome formation of human placental EVTs: Insights into recurrent spontaneous abortion.Genes & diseases · 2025Article
- Article
- Mechanometabolism: recent findings on the intersection of cell adhesion, cell migration, and metabolism.American journal of physiology. Cell physiology · 2025Review
- Trpv4-mediated mechanotransduction regulates the differentiation of valvular interstitial cells to myofibroblasts: implications for aortic valve stenosis.American journal of physiology. Cell physiology · 2025Article
- A novel approach for engineering DHCM/GelMA microgels: application in hepatocellular carcinoma cell encapsulation and chemoresistance research.Frontiers in bioengineering and biotechnology · 2025Article
- Zymogen granule protein 16B (ZG16B) is a druggable epigenetic target to modulate the mammary extracellular matrix.Cancer science · 2025Article
- Bilayer 3D co-culture platform inducing the differentiation of normal fibroblasts into cancer-associated fibroblast like cells: New in vitro source to obtain cancer-associated fibroblasts.Bioengineering & translational medicine · 2025Article
- Tissue-dependent mechanosensing by cells derived from human tumors.npj biological physics and mechanics · 2025Article
- Insights into the mechanisms, regulation, and therapeutic implications of extracellular matrix stiffness in cancer.Bioengineering & translational medicine · 2025Review
- Cancer-associated fibroblasts: heterogeneity, tumorigenicity and therapeutic targets.Molecular biomedicine · 2024Review
- Leader Cells: Invade and Evade-The Frontline of Cancer Progression.International journal of molecular sciences · 2024Review
- Extracellular matrix regulation of cell spheroid invasion in a 3D bioprinted solid tumor-on-a-chip.Acta biomaterialia · 2024Article
- Asymmetric crowders and membrane morphology at the nexus of intracellular trafficking and oncology.Mechanobiology in medicine · 2024Article
- Human Platelet Lysate-Derived Nanofibrils as Building Blocks to Produce Free-Standing Membranes for Cell Self-Aggregation.ACS nano · 2024Article
- Integrating integrins with the hallmarks of cancer.Matrix biology : journal of the International Society for Matrix Biology · 2024Review
- Effect of Hydrogel Stiffness on Chemoresistance of Breast Cancer Cells in 3D Culture.Gels (Basel, Switzerland) · 2024Article
- Mechanosensitive hormone signaling promotes mammary progenitor expansion and breast cancer risk.Cell stem cell · 2024Article
68 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors.
Funding
Abstract
Extracellular matrix (ECM) stiffness induces focal adhesion assembly to drive malignant transformation and tumor metastasis. Nevertheless, how force alters focal adhesions to promote tumor progression remains unclear. Here, we explored the role of the focal adhesion protein vinculin, a force-activated mechanotransducer, in mammary epithelial tissue transformation and invasion. We found that ECM stiffness stabilizes the assembly of a vinculin-talin-actin scaffolding complex that facilitates PI3K-mediated phosphatidylinositol (3,4,5)-triphosphate phosphorylation. Using defined two- and three-dimensional matrices, a mouse model of mammary tumorigenesis with vinculin mutants, and a novel super resolution imaging approach, we established that ECM stiffness, per se, promotes the malignant progression of a mammary epithelium by activating and stabilizing vinculin and enhancing Akt signaling at focal adhesions. Our studies also revealed that vinculin strongly colocalizes with activated Akt at the invasive border of human breast tumors, where the ECM is stiffest, and we detected elevated mechanosignaling. Thus, ECM stiffness could induce tumor progression by promoting the assembly of signaling scaffolds, a conclusion underscored by the significant association we observed between highly expressed focal adhesion plaque proteins and malignant transformation across multiple types of solid cancer. See all articles in this Cancer Research section, "Physics in Cancer Research."
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