Mechanical compression drives cancer cells toward invasive phenotype
Open accessAbstract
Uncontrolled growth in a confined space generates mechanical compressive stress within tumors, but little is known about how such stress affects tumor cell behavior. Here we show that compressive stress stimulates migration of mammary carcinoma cells. The enhanced migration is accomplished by a subset of “leader cells” that extend filopodia at the leading edge of the cell sheet. Formation of these leader cells is dependent on cell microorganization and is enhanced by compressive stress. Accompanied by fibronectin deposition and stronger cell–matrix adhesion, the transition to leader-cell phenotype results in stabilization of persistent actomyosin-independent cell extensions and coordinated migration. Our results suggest that compressive stress accumulated during tumor growth can enable coordinated migration of cancer cells by stimulating formation of leader cells and enhancing cell–substrate adhesion. This novel mechanism represents a potential target for the prevention of cancer cell migration and invasion.
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- Authors
- Tse, J. M., Cheng, G., Tyrrell, J. A., Wilcox-Adelman, S. A., Boucher, Y., Jain, R. K., & Munn, L. L.
- Affiliations
- Harvard University (US)
- Boston Biomedical Research Institute, Watertown, MA 02472
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2011-12-27
- Volume
- 109
- Issue
- 3
- Pages
- 911-916
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC3271885
- OpenAlex
- W2062664804
- Semantic Scholar
- a2dbeb0662e18800f3401823b4d884358acfe777
- Cited by
- 631
- References
- 51
- Citations by year
- 2026: 39 · 2025: 48 · 2024: 59 · 2023: 57 · 2022: 38 · 2021: 56 · 2020: 58 · 2019: 66 · 2018: 49 · 2017: 42 · 2016: 35 · 2015: 28 · 2014: 27 · 2013: 18 · 2012: 10
- FWCI
- 8.44
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc)
- Funders
- National Heart, Lung, and Blood Institute (R56HL064240, R01HL064240, HL64240)
- National Cancer Institute (P01CA080124)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Physical Sciences › Mathematics › Modeling and Simulation › Mathematical Biology Tumor Growth
- Keywords
- compressive stress, tumor microenvironment, tumor cell migration, leader cells, filopodia, breast cancer, cell sheets, cell-matrix adhesion, fibronectin deposition, tumor invasion, mechanical stress
- MeSH terms
- Actomyosin, Breast Neoplasms, Cell Adhesion, Cell Movement, Cytoskeleton, Female, Humans, Models, Biological, Neoplasm Invasiveness, Phenotype, Pseudopodia, Stress, Mechanical, Cell-Matrix Junctions, Cell Line, Tumor
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