ArticleProceedings of the National Academy of Sciences of the United States of America2021
Matrix stiffness drives stromal autophagy and promotes formation of a protumorigenic niche.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.
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Who cites it
64 citing papers in PubMed, 92 citations in OpenAlex.
- Substrate stiffness regulates HIF-1α signalling via β1-integrin/myosin-2/NF-κB axis.Journal of translational medicine · 2026Article
- Mechanical Signaling From ECMs to Nuclear Envelopes in Cell Transitions and Fate Decisions: A Review and Perspective on Adhesion-Niche-Based Anti-EndMT and Anti-EMT.Annals of biomedical engineering · 2026Review
- Macrophage-derived fibronectin suppresses antitumor immunity via tissue stiffening and immunosuppressive cell induction in cancer mouse models.Nature communications · 2026Article
- Mechanical-biochemical signaling accelerates scleral remodeling in myopia via the LaminA/C-Emerin-MKL1 axis.Cell communication and signaling : CCS · 2026Article
- PIEZO1 enhances pancreatic cancer neurotropism.Cancer cell international · 2026Article
- Deciphering Stiffness-Driven Changes in Colorectal Cancer by Proteomics.Molecular & cellular proteomics : MCP · 2026Article
- Critical Roles and Molecular Mechanisms of Chaperone-Mediated Autophagy in Infections.International journal of molecular sciences · 2026Review
- Extracellular matrix stiffness in hepatocellular carcinoma: mechanisms and targeted therapeutic strategies.Frontiers in immunology · 2026Review
- Cryoelectrospun Elastin-Alginate Scaffolds Support In Vitro 3D Epithelial-Stromal Cocultures for Salivary Tissue Engineering.Gels (Basel, Switzerland) · 2025Article
- Myosin-actin pattern links matrix stiffness to GFAT2-hyaluronan metabolism.Materials today. Bio · 2025Article
- Matrix Stiffness Promotes DRP1-Mediated Myofibroblast Senescence to Drive Silica-Induced Pulmonary Fibrosis.Aging cell · 2025Article
- Characterization of Corneal Defects in ATG7-Deficient Mice.International journal of molecular sciences · 2025Article
- Mechanometabolism: recent findings on the intersection of cell adhesion, cell migration, and metabolism.American journal of physiology. Cell physiology · 2025Review
- Identification of Cancer Associated Fibroblasts Related Genes Signature to Facilitate Improved Prediction of Prognosis and Responses to Therapy in Patients with Pancreatic Cancer.International journal of molecular sciences · 2025Article
- Macrophages and fibroblasts as regulators of the immune response in pancreatic cancer.Nature immunology · 2025Review
- Unlocking the crucial role of cancer-associated fibroblasts in tumor metastasis: Mechanisms and therapeutic prospects.Journal of advanced research · 2025Review
- Integrating bioengineering, super-resolution microscopy and mechanobiology in autophagy research: addendum to the guidelines (4th edition).Autophagy · 2025Article
- FAK and p130Cas Modulate Stiffness-Mediated Early Transcription and Cellular Metabolism.Cytoskeleton (Hoboken, N.J.) · 2025Article
- Review
- Assessment of Stiffness-Dependent Autophagosome Formation and Apoptosis in Embryonal Rhabdomyosarcoma Tumor Cells.Methods in molecular biology (Clifton, N.J.) · 2025Article
4 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Increased stiffness of solid tissues has long been recognized as a diagnostic feature of several pathologies, most notably malignant diseases. In fact, it is now well established that elevated tissue rigidity enhances disease progression and aggressiveness and is associated with a poor prognosis in patients as documented, for instance, for lung fibrosis or the highly desmoplastic cancer of the pancreas. The underlying mechanisms of the interplay between physical properties and cellular behavior are, however, not very well understood. Here, we have found that switching culture conditions from soft to stiff substrates is sufficient to evoke (macro) autophagy in various fibroblast types. Mechanistically, this is brought about by stiffness-sensing through an Integrin αV-focal adhesion kinase module resulting in sequestration and posttranslational stabilization of the metabolic master regulator AMPKα at focal adhesions, leading to the subsequent induction of autophagy. Importantly, stiffness-induced autophagy in stromal cells such as fibroblasts and stellate cells critically supports growth of adjacent cancer cells in vitro and in vivo. This process is Integrin αV dependent, opening possibilities for targeting tumor-stroma crosstalk. Our data thus reveal that the mere change in mechanical tissue properties is sufficient to metabolically reprogram stromal cell populations, generating a tumor-supportive metabolic niche.
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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.