Genetic Switch Could Halt The Spread Of Cancer, Research Suggests


Flipping a genetic switch in tumour cells can halt the spread of cancer, scientists have shown.

The discovery raises the possibility of stopping deadly disease in its tracks by blocking the gene, thought to be active in all aggressive cancers.

HGMA1 operates like an orchestra conductor, regulating a range of biological processes tumours need to grow and spread around the body.

Its usual role is to drive cell growth during embryonic development. In healthy adult cells, it is turned off, but the gene is reactivated in cancers.

In laboratory tests, scientists found that suppressing HGMA1 in highly aggressive breast cancer caused the tumour cells to look much more normal and healthy. Their growth was greatly slowed and they stopped migrating and invading new territory.

Breast tumours implanted into mice were far less likely to grow and spread when HGMA1 was blocked.

Dr Linda Resar, from Johns Hopkins University School of Medicine in Baltimore, US, said : "This master regulator is normally turned off in adult cells, but it is very active during embryonic development and in all highly aggressive tumors studied to date.

"Our work shows for the first time that switching this gene off in aggressive cancer cells dramatically changes their appearance and behavior."

HGMA1 plays a role in reprogramming ordinary mature cells into stem cells that can transform themselves into any kind of tissue. One of the major hurdles facing stem cell scientists is the risk of generating tumours by triggering out-of-control cell growth.

The new work developed from research investigating the behaviour of HGMA1 in stem cells.

Dr Resar's team, whose findings are reported in the online journal Public Library of Science ONE, studied the gene in several strains of human breast cancer. They included "triple negative" cancers that are extremely aggressive and hard to


"The aggressive breast cancer cells grow rapidly and normally appear spindle-shaped or thin and elongated," said Dr Resar. "Remarkably, within a few days of blocking HMGA1 expression, they appeared rounder and much more like normal breast cells growing in culture."

Unlike their cousins in which the gene was active, the cells grew very slowly and tended to stay in one place.

Study leader Dr Sandeep Shah, also from Johns Hopkins, said: "From previous work, we know that HMGA1 turns on many different genes needed during very early development, but it's normally turned off by the time we're born.

"Flipping that master regulator back on seems to be necessary for a cancer to become highly aggressive, and now we've seen that flipping HMGA1 off again can reverse that aggressive behaviour."

The scientists are now taking the first steps towards developing a cancer treatment based on their research. Working with other Johns Hopkins scientists, they are looking at ways of safely delivering HMGA1-blocking molecules into tumours.

Another approach might be not to suppress the gene itself, but one of the pathways it affects, said Dr Resar.