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. While the scope of cancer is enormous, the answer to more effective treatments may be hidden within a microscopic cell.
Led by Texas A&M University graduate students Samere Zade of the department of biomedical engineering and Ting-Ching Wang of the department of chemical engineering, a paper published by Lele Lab has uncovered new details about the mechanism behind the progression of cancer.
Published in Nature CommunicationsThe article explores the influence that mechanical toughening 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 allow tumor progression are not understood,” said Dr. Tanmay Lele, joint professor in the departments of biomedical engineering and chemical engineering. “Our findings shed new light on how hardening of tumor tissue can promote tumor cell proliferation.”
In the paper, the researchers reveal that when a cell is faced with a rigid environment, the nuclear lamina (the scaffolding that helps the nucleus maintain its shape and structure) becomes taut and wrinkle-free as the cell stretches over the surface. rigid surface. This spread causes yes-associated protein (YAP), the protein that regulates cell multiplication, to move to the nucleus.
That localization can lead to greater 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 stiff tissues,” Zade said.
These findings build on Lele’s earlier discovery that the cell nucleus behaves like a drop of liquid. In that work, the researchers found that a protein in the nuclear lamina called lamin A/C helps maintain the surface tension of the nucleus. In the most recent study, reducing lamin A/C levels was found to decrease YAP localization, which in turn decreases rapid cell proliferation.
“The lamin A/C protein plays a key role here: reducing it makes cells less responsive to environmental rigidity, particularly affecting the localization of a key regulatory protein (YAP) in the nucleus,” Zade explained.
Although seemingly complex and specialized, Zade and Lele believe the broader implications of their discovery may guide future cancer treatments.
“Discovering how matrix stiffness drives nuclear changes and regulates key pathways, such as YAP signaling, opens the door to developing therapies targeting these mechanistic pathways,” Zade explained. “Drugs or treatments could be designed to soften the tumor environment, altering the physical signals that help cancer cells thrive. Lamin A/C and related nuclear mechanics could become targets for cancer treatments.”
In the future, the Lele Laboratory aims to investigate the extent to which its discoveries apply to tumors derived from patients.
For this work, the Lele Laboratory was funded by the National Institutes of Health, the Texas Cancer Prevention and Research Institute, 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.