Microscopic discovery reveals how cancer cells grow faster

Have you ever wondered how malignancies like cancer grow, evolve, and, most importantly, how we can stop them? The answer may be hidden within the microscopic world of our cells.

This year, the World Health Organization has reported that cancer afflicted over 20 million people and claimed nearly 10 million lives. The search for an effective cure is a race against time, and two bright minds from Texas A&M University have brought us a step closer to the finish line.

Environment around cancer cells

Graduate students Samere Zade and Ting-Ching Wang from Texas A&M University, working under the guidance of the Lele Lab, have uncovered valuable insights into cancer’s progression.

The research, published in the journal Nature Communications, reveals how the stiffening of a tumor cell’s environment influences the structure and function of its nucleus. This offers a new perspective on why cancer cells proliferate so aggressively.

“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,” explained Dr. Tanmay Lele, a joint faculty member in biomedical and chemical engineering.

“Our findings shed new light into how the stiffening of tumor tissue can promote tumor cell proliferation.”

Stiffness and cancer cell proliferation

The study highlights how tumor cells respond to stiff surroundings. The nuclear lamina, which is like a support structure for the cell’s nucleus, becomes smoother and tighter when the cell interacts with a stiff environment.

This happens because the cell spreads out on the rigid surface, causing changes in the nucleus’s structure.

As a result, a specific protein called yes-associated protein (YAP) moves into the nucleus. YAP plays a crucial role in controlling how cells multiply. Once inside the nucleus, YAP activates processes that make the cancer cells grow and divide more rapidly, contributing to the aggressive spread of the tumor.

“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,” said Zade.

Structural integrity of the cell nucleus

This discovery expands on earlier research by the Lele Lab, which showed that the cell nucleus acts similarly to a liquid droplet. Just like a droplet maintains its shape due to surface tension, the nucleus relies on a protein called lamin A/C in its nuclear lamina to preserve its structural integrity.

In the new study, researchers found that lamin A/C not only helps maintain the nucleus shape but also plays a key role in regulating cancer cell growth.

When lamin A/C levels are reduced, it disrupts the ability of the yes-associated protein (YAP) to move into the nucleus.

Since YAP is responsible for promoting cell multiplication, this reduction in lamin A/C limits YAP activity in the nucleus, slowing down the rapid proliferation of cancer cells. This finding suggests that lamin A/C could be a potential target for cancer treatments.

“The protein lamin A/C plays a key role here – reducing it made cells less responsive to environmental stiffness, particularly affecting the localization of a key regulatory protein (YAP) to the nucleus,” Zade explained.

Implications for cancer treatments

The implications of this research extend beyond academic understanding. By uncovering how matrix stiffness drives nuclear changes and regulates pathways like YAP signaling, the findings open the door to innovative cancer treatments.

“Uncovering how matrix stiffness drives nuclear changes and regulates key pathways, like YAP signaling, opens the door to developing therapies that target these mechanical pathways,” said Zade.

“Drugs or treatments could be designed to soften the tumor environment, disrupting the physical cues that help cancer cells thrive. Lamin A/C and related nuclear mechanics could become targets for cancer treatments.”

Future research directions

The Lele Lab plans to expand its research by investigating the extent to which these findings apply to tumors derived from patients. This step could bridge the gap between lab-based discoveries and practical treatments, bringing hope to millions affected by cancer.

This work was supported by the National Institutes of Health, the Cancer Prevention and Research Institute of Texas, and the National Science Foundation. The Texas A&M Engineering Experiment Station administered the funding, highlighting the institution’s commitment to innovative cancer research.

Through their meticulous study of nuclear mechanics and tumor stiffness, the researchers at the Lele Lab have paved the way for new avenues in cancer treatment.

The findings highlight the importance of targeting the physical microenvironment of cancer cells, offering a fresh perspective in the fight against one of humanity’s most challenging diseases.

The study is published in the journal Nature Communications.

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