Cited by 631Cellular Mechanics and InteractionsCancer Cells and MetastasisMathematical Biology Tumor Growth

Mechanical compression drives cancer cells toward invasive phenotype

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Tse, Janet M., Cheng, Gang, Tyrrell, James A., Wilcox-Adelman, Sarah A., Boucher, Yves, Jain, Rakesh K., Munn, Lance L.·2012·Proceedings of the National Academy of Sciences

Abstract

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
Published
2011-12-27
Volume
109
Issue
3
Pages
911-916
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
OpenAlex
W2062664804
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
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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