In 2022 alone, more than 20 million people were diagnosed with cancer and nearly 10 million died from the disease, according to the World Health Organization. Although the cancer burden is immense, the answer to more effective treatments may be hidden in a microscopic cell.
Led by Texas A&M University graduate students Samere Zade in the Department of Biomedical Engineering, and Ting-Ching Wang in the Department of Chemical Engineering, a paper published by the Lele Lab revealed new details about the mechanism behind the cancer progression.
Published in Natural communicationsThe article explores the influence that mechanical stiffening of the tumor cell environment can have on the structure and function of the nucleus.
Cancer has proven to be a difficult disease to treat. It is extremely complex and the molecular mechanisms that enable tumor progression are not understood. Our findings shed new light into how stiffening tumor tissue can promote the proliferation of tumor cells. »
Dr. Tanmay Lele, Joint Professor of the Departments of Biomedical Engineering and Chemical Engineering, Texas A&M University
In the article, the researchers reveal that when a cell is confronted with a rigid environment, the nuclear lamina –; a scaffold that helps the core maintain its shape and structure –; becomes smooth and taut as the cell spreads across the rigid surface. This spread causes yes-associated protein (YAP), the protein that regulates cell multiplication, to move toward the nucleus.
This localization may lead to increased cell proliferation, which may explain the rapid growth of cancer cells in rigid environments.
“The ability of stiff matrices to influence nuclear tension and regulate YAP localization could help explain how tumors become more aggressive and perhaps even resistant to treatment in stiffened tissues,” Zade said.
These findings build on Lele's previous discovery that the cell nucleus behaves like a liquid droplet. In this work, researchers discovered that a nuclear lamina protein called lamin A/C helps maintain the surface tension of the nucleus. In the most recent study, it was found that reducing lamin A/C levels decreases YAP localization, thereby decreasing rapid cell proliferation.
“The lamin A/C protein plays a key role here: its reduction made cells less sensitive to environmental stiffness, particularly affecting the localization of a key regulatory protein (YAP) in the nucleus,” explained Zade.
Although seemingly complex and specialized, Zade and Lele believe the broader implications of their discovery could guide future cancer treatments.
“Uncovering how matrix stiffness drives nuclear changes and regulates key pathways, such as YAP signaling, opens the door to developing therapies targeting these mechanical pathways,” Zade explained. “Drugs or treatments could be designed to soften the tumor environment, disrupting the physical signals that help cancer cells grow. Lamin A/C and associated nuclear mechanics could become targets for cancer treatments. »
In the future, the Lele Lab aims to study the extent to which their findings apply to patient-derived tumors.
For this work, the Lele Lab was funded by the National Institutes of Health, the Cancer Prevention and Research Institute of Texas, and the National Science Foundation. Funding for this research is administered by the Texas A&M Engineering Experiment Station, the official research agency of Texas A&M Engineering.
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