When a cancerous tumour breaks out and spreads to other sites in the body, it is often bad news for the patient. But researchers at University College Dublin (UCD) and the Mater Misericordiae Hospital have now discovered that a particular gene helps stomach cancers to invade or burrow through tissue, one of the first steps allowing it to spread, writes Dr Claire O'Connell.
They hope their breakthrough will ultimately help deliver treatments to keep cancer cells in the one place so that they can be more easily treated or removed.
Stomach or gastric cancer is one of the most common causes of cancer-related deaths in the world. Patients tend to seek medical help when the cancer is at a late stage, which is a problem, says Dr Peter Doran, director of the general clinical research unit at the Mater. In addition, stomach cancers tend to invade and form secondary tumours in other parts of the body.
This is why the UCD-Mater group decided to focus on what makes a stomach cancer invasive, explains Doran. First they did some burrowing of their own - into online databases that catalogue what genes are switched on in particular tissues. When they compared the readouts from normal stomach tissue and gastric cancer, a couple of genes caught their eye, including one called Net1.
They followed up the leads by collecting and testing tissue from patients undergoing surgery for gastric cancer at the Mater, gathering both a tumour sample and a matched normal sample from a couple of centimetres outside the margins of the tumour.
Their experiments showed that the Net1 gene was clearly switched on in cancerous cells, and that observation led to more in-depth questions, says Doran.
"We were interested in more than a quantitative study of just showing that this gene is different, because that's not contributing anything new for the patient," he says. "We wanted to look at what the gene does, and more importantly, is there potential to stop it doing what it does."
They knew the Net1 gene made a protein that helped to regulate another protein, RhoA, which is central to many important processes in the cell including rapid growth and death. And they figured that Net1 was inappropriately activating RhoA, leading to the cells having cancerous characteristics.
To silence Net1 in cancer cells in the lab, the researchers stuck specially engineered stretches of genetic material onto the working copies of the gene and blocked it from being turned into a protein.
The result? Taking Net1 out of the equation stopped the cancer cells rapidly growing and invading. "This was a significant finding," says Doran of the results, which the group published earlier this year in the British Journal of Cancer.
Now they are looking at what Net1 does in normal cells, seeking out potential avenues to stop Net1 from activating RhoA in a way that prompts cells to turn invasive.
The ultimate hope is that by stopping invasion, treatment becomes easier. "If we can stop a tumour invading we will restrict it to a local event which can be surgically resected," says Doran. "That has been our focus as opposed to trying to kill the tumour completely."
They also want to see if Net1 could serve as a useful "biomarker" to tell doctors whether a tumour is at risk of becoming invasive, he adds.
And Dr Doran believes their findings will have implications for other cancers including tumours of the colon or breast. "Initially we looked at Net1 as a gastric cancer-associated protein but our thinking now is moving wider," he says. "We are very excited about the potential for this gene both as a biomarker and as a therapeutic target and it's good to examine that across lots of tumour types."