New research has found that the enzyme EZH2 drives chaotic cell divisions and fuels cancer metastasis by silencing key genes. The discovery opens the door to new therapies.
A Weill Cornell Medicine innovator published in Cancer Discovery has identified a crucial mechanism that drives propagation of triple negative breast cancer (TNBC), one of the most aggressive and treatment-resistant forms.
The investigation reveals that a enzyme called EZH2 fuels abnormal cell division, allowing cancer cells to metastasize, or spread, to distant organs.
The team found that drugs that block EZH2 can help restore normal cell division and stopping metastasis in preclinical models.
“Metastasis is the main reason why patients with triple-negative breast cancer face a low chance of survival,” he explains. Vivek mittalresearcher at Weill Cornell Medicine and leader of the study. “Our study suggests a new therapeutic approach to block metastasis before it takes hold and help patients overcome this deadly cancer.”
CMTN lacks three common hormone receptors that other breast cancers rely on for targeted therapies, leaving chemotherapy as the main option.
Approximately 5% of TNBC tumor cells are highly prone to metastasis. These cells have chromosomal instability and epigenetic changes, which affect the way genes are expressed without altering the DNA itself.
Mittal’s team identified EZH2 as the key link between these processes. Normally, EZH2 helps regulate DNA packaging, but in TNBC it becomes hyperactive, silencing genes that ensure proper chromosome division.
When this happens, the cells begin to divide incorrectlyproducing daughter cells with serious genetic errors that make them more invasive, explains .
Using patient data, researchers found that higher levels of EZH2 were correlated with more chromosomal abnormalities. Laboratory experiments later confirmed that inhibiting EZH2 with the cancer drug tazemetostat stabilized chromosome segregation and reduced metastasis in murine models.
The researchers also discovered that EZH2 interrupts cell division by silencing the tankyrase 1 gene, leading to an excess of another protein, CPAP, which causes the uncontrolled duplication of centrosomes, the structures that separate chromosomes. The result is the chromosomal chaos and aggressive tumor growth.
The team now plans to explore clinical trials using EZH2 inhibitors to prevent metastasis in triple-negative breast cancer (TNBC) and other cancers marked by similar chromosomal instability.
