Genetic 'switch' could halt aggressive cancer growth

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Cancer cells with active (left) and inactive (right) HMGA1 genes--Courtesy of Sandeep Shah, Johns Hopkins Medicine

Flipping a genetic switch in cancer cells may put the brakes on tumor growth, according to new research from Johns Hopkins University School of Medicine.

Researchers at Johns Hopkins have identified a gene that, when repressed in tumor cells, stopped cell growth and a range of processes needed for tumors to grow and metastasize. This so-called regulatory switch--which is normally turned off in adult cells but active in embryonic development and in highly aggressive tumors--could help scientists develop better therapies for drug-resistant tumors.

A team led by Dr. Linda Resar, an associate professor of medicine, oncology and pediatrics, and affiliate in the Institute for Cell Engineering at Johns Hopkins Medicine, previously developed techniques to block the HMGA1 gene in stem cells in order to study its role in those cells. In past studies, they discovered that HMGA1 is essential for reprogramming adult cells, like blood or skin cells, into stem cells that share most, if not all, properties of embryonic stem cells.

In the new study, Resar's team blocked HMGA1 expression in aggressive breast cancer cells and tracked their appearance and growth patterns.

"The aggressive breast cancer cells grow rapidly and normally appear spindle-shaped or thin and elongated. Remarkably, within a few days of blocking HMGA1 expression, they appeared rounder and much more like normal breast cells growing in culture," Resar said in a statement. Researchers also observed that cells with suppressed HMGA1 grew very slowly and did not spread to other parts of the body.

In mice, tumors with HMGA1 grew and spread to other areas, such as the lungs, but those with blocked HMGA1 did not grow well in the breast tissue or spread to other sites, essentially reversing aggressive tumor behavior.

Resar said the next step would be to develop a therapy based on their early research. The team is working with other researchers at Johns Hopkins to test whether HMGA1-blocking molecules could be delivered to tumors inside nanoparticles. Another possible therapeutic approach would be to block one of the pathways or processes that HMGA1 affects instead of the gene itself.

- read the press release
- check out the study

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