- Brendan Sullivan, Taylor Light, Vinh Vu, Adrian Kapustka, Kalina Hristova, Deborah Leckband. Mechanical disruption of E-cadherin complexes with epidermal growth factor receptor actuates growth factor–dependent signaling. Proceedings of the National Academy of Sciences, 2022; 119 (4): e2100679119 DOI: 10.1073/pnas.2100679119
The study, led by chemical and biomolecular engineering professor Deborah Leckband, found that cadherins that bond with growth factor receptors can sense mechanical force and respond by altering cell communication and growth.
The findings are published in the Proceedings of the National Academy of Sciences.
When bound to cadherin molecules in normal tissue, growth factor receptors cannot communicate with growth factor proteins — the substance they need to promote tissue growth. However, the study shows that changes in tensional stress on cadherin bonds disrupt the cadherin-growth factor interaction to switch on growth signals in tissues.
To demonstrate how tension influences tissue growth, the researchers set up an experiment to observe how in vitro human carcinoma cells convert mechanical information into biochemical signals, Leckband said.
The team used a self-built “cell stretcher” in which the carcinoma cells are grown in a thin layer on the surface of a flexible medium. When the cells are stretched, the researchers observed changes that could increase tissue growth and tumorigenesis.
“This study confirms that cadherins use force to switch on biochemical growth signaling,” Leckband said. “By confirming these force-induced disruptions, we may be able to find a way to mutate cadherin molecules in order to prevent certain types of tissue growth, such as metastatic transformation and tumorigenesis.”
The team has observed the cadherin-growth factor receptor complex in human epithelial tissue and plans to expand this concept by working with in vitro human breast tissue.
Illinois graduate students Brendan Sullivan and Vinh Vu; undergraduate student Adrian Kapustka; and researchers from Johns Hopkins University contributed to this study.
Leckband also is a professor of chemistry and of bioengineering, and is affiliated with the Beckman Institute for Advanced Science and Technology, the Carl R. Woese Institute for Genomic Biology and the Nick Holonyak Micro and Nanotechnology Laboratory.
The National Institutes of Health supported this study.
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Cellular proteins enable tissues to sense, react to mechanical force