Researchers at Columbia University have found a molecule that is responsible for arousing dormant cells from breast cancer and nudging them to create metastases. Silencing this molecule, called Malat1, in mice with breast cancer reduced metastases and improved survival, suggesting that a similar treatment could benefit patients.
Cancer dormancy In recent years, cancer researchers have come to understand that early in tumor development, some cancer cells escape the primary tumor, travel to distant parts of the body, and hibernate, only to awaken years or even decades later to form metastases.
What controls this phenomenon—known as cancer dormancy—is poorly understood. But because metastases cause most cancer-related deaths, better insights into dormancy could lead to substantial improvements in treatment.
A double shot for wakening Malat1, previously associated with a variety of cancers, is a long noncoding RNA (lncRNA), a type of RNA with diverse roles in gene regulation.
In a previous study of mice, the researchers conducted a genetic screen to uncover factors that might contribute to the reactivation of dormant metastatic breast cancer cells. One of the most compelling “hits” was Malat1.
Want more breaking news? Subscribe to Technology Networks ’ daily newsletter, delivering breaking science news straight to your inbox every day.
Subscribe for FREE
The researchers then examined how Malat1 works.
“We found that Malat1 exerts a double whammy in dormant cancer cells. First, it activates gene expression pathways that wake the cells up and makes them more likely to proliferate and form new tumors. Second, Malat1 stimulates the production of molecules that block the immune system from recognizing and destroying the newly activated cancer cells,” says Benjamin Izar, MD, PhD , a co-leader of the study and assistant professor of medicine at Columbia University Vagelos College of Physicians and Surgeons.
“In other words, Malat1 affects the behavior of the dormant cancer as well as the surrounding tumor microenvironment,” adds Dhiraj Kumar, PhD, associate research scientist in genetics & development and the study’s lead author.
Putting cells back to sleep
“In our mouse model of breast cancer, the administration of ASOs dramatically reduced the development of lung metastases,” Kumar says. Such drugs could potentially prevent or treat metastases in other cancers, Kumar adds, since Malat1 appears to play a role in the metastasis of colon, lung, and skin cancer.
Still unknown is the initial factor that leads to greater Malat1 expression.
“It is difficult to say, but one variable that confers cumulative risk for reactivation is time,” Izar says. “Dormant cancer cells probably awaken all the time, but they get recognized by the immune system and then destroyed. This protective effect may weaken with aging.”
Reference: Kumar D, Gurrapu S, Wang Y, et al. LncRNA Malat1 suppresses pyroptosis and T cell-mediated killing of incipient metastatic cells. Nat Cancer . 2024. doi: 10.1038/s43018-023-00695-9
This article has been republished from the following materials. Note: material may have been edited for length and content. For further information, please contact the cited source.
Add Technology Networks as a preferred Google source to see more of our trusted coverage.
