Dynamically stiffened matrix promotes malignant transformation of mammary epithelial cells via collective mechanical signaling
Abstract
Gradual stiffening of the native extracellular matrix has been implicated in promoting breast cancer progression through stiffness-mediated signaling. Herein, we probe mammary epithelial cell responses to substrate stiffness with a dynamically stiffened hydrogel, enabling investigation of how the change in substrate stiffness impacts collective cell behaviors. We demonstrate that signaling pathways, both paracrine and mechanosensing, impact mammary epithelial cell response to stiffening and act in concert to drive epithelial-mesenchymal plasticity. Interestingly, previous static stiffness hydrogel studies did not observe this interplay of signaling, highlighting the need for dynamic materials to recapitulate disease development. These responses can also be inhibited, individually and together, demonstrating how dynamic stiffening drives cancer progression.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Feb 12, 2019
- Source ID
- 10.1073/pnas.1814204116
Entities
People
- Adam J Engler
- Aditya Kumar
- Bibiana F. Matte
- Christopher M. Plunkett
- Jesse K Placone
- Jing Yang
- Kirsten C. Wong
- Laurent Fattet
- Matthew G. Ondeck
Organizations
- Achievement Rewards for College Scientists Foundation
- Federal University of Rio Grande do Sul
- National Institutes of Health
- National Science Foundation
- Sanford Consortium for Regenerative Medicine
- United States Department of Defense
- University of California, San Diego