A new study identifies the EZH2 "chaos enzyme" as a key driver of metastasis in triple-negative breast cancer. Researchers found that inhibiting this enzyme restores order to cell division, offering a promising new strategy to halt the spread of this aggressive cancer.
October 4, 2025
Source:
Medical Xpress
Enzyme Drives Cancer Spread by Inducing Chaos
Researchers at Weill Cornell Medicine have identified a critical enzyme that fuels the spread of triple-negative breast cancer (TNBC), one of the most aggressive forms of the disease. The enzyme, EZH2, promotes metastasis by creating chaos during cell division.
This finding offers a new target for therapies aimed at preventing the spread of cancer, which is the leading cause of death for TNBC patients.
The Mechanism of Chaos
EZH2 is an epigenetic enzyme that functions by silencing other genes. The study revealed its specific role in TNBC progression:
Gene Silencing: EZH2 targets and silences the tankyrase 1 gene, which is essential for orderly chromosome separation during cell division.
Protein Buildup: When tankyrase 1 is silenced, a protein called CPAP accumulates, causing cellular structures known as centrosomes to multiply abnormally.
Flawed Division: These extra centrosomes disrupt cell division, leading to new cancer cells with abnormal numbers of chromosomes—a condition called chromosomal instability.
This instability allows cancer cells to rapidly evolve, adapt, and invade distant organs, a hallmark of metastatic cancer. According to the National Cancer Institute, metastasis is the primary reason breast cancer becomes fatal.
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Restoring Order to Stop Metastasis
The study marks a significant paradigm shift in cancer treatment strategy. While some previous approaches aimed to increase chromosomal chaos to kill cancer cells, this research demonstrates that restoring order is more effective at preventing their spread.
By inhibiting EZH2, the research team was able to reverse the process.
A New Therapeutic Avenue
Using preclinical models, the scientists showed that blocking EZH2 with specific inhibitors had a profound effect:
It restored the function of the tankyrase 1 gene.
It allowed for normal, orderly chromosome segregation during cell division.
It sharply reduced the cancer cells' ability to metastasize.
This suggests that targeting EZH2 doesn't just attack the primary tumor but, more critically, it cripples the cancer's ability to spread throughout the body. The findings open the door for new clinical trials for high-risk breast cancer patients.
Repurposing an Existing Drug
An FDA-approved drug already exists that inhibits EZH2. Tazemetostat, used to treat other cancers, was shown to be effective in the study's models. Repurposing this drug could accelerate its translation into clinical use for TNBC patients.
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Source:
Nature
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