Bowel cancer cells FLIP out

One of our top bowel cancer bods, Professor Paddy Johnston, had a paper out in the journal Cancer Research recently.

We were first drawn to blog about it by the name of the gene and the obvious puns to be had from it, but there’s some seriously interesting science underneath.

Cancer starts when a cell in the body starts multiplying our of control. But as well as thinking of cancer cells as multiplying too much, they are also faulty cells that don’t know they should die. Controlled cell death – known as apoptosis – is vital for helping to keep our bodies healthy.

For example, our skin cells die if they are damaged by sunlight – you can see this as peeling if you’ve ever been badly sunburnt. But if cells are damaged and don’t die, then they can carry on multiplying – leading to cancer.

When cells need to die, a molecular cascade of events is triggered. Eventually, molecules called caspases are activated. These chop up proteins within the cell, and also activate other proteins that hack up the cell’s DNA. The cell is literally chopped up from the inside out, and the remains are eaten up by scavenger cells.

c-FLIP is a molecule that stops the activation of a specific caspase called caspase-8, blocking the cell death process. Researchers have previously found high levels of the c-FLIP in bowel cancers, compared with healthy tissue. So scientists are pretty interested in finding out if c-FLIP could potentially be targeted as a treatment for cancer.

Here’s where Professor Paddy Johnston and his team at Queen’s University in Belfast some in. Using a technique called RNAi, the researchers reduced the levels of c-FLIP in bowel cancer cells grown in the lab. They found that large numbers of treated cells died, suggesting that removing c-FLIP has activated cell death. But that’s just cells in the lab, and we all know that petri dishes aren’t exactly the same as real life situations.

So the scientists went on to use RNAi to reduce c-FLIP levels in human bowel cancer cells transplanted into mice. The team found that using c-FLIP-specific RNAi could slow down the growth of tumours, but nonsense “scrambled” RNAi had no significant effect.

Finally, the scientists also found that adding in extra c-FLIP reduced the levels of cell death in transplanted bowel cells. They also showed that the c-FLIP boosted cells are also more resistant to a combination of commonly used bowel cancer drugs. So maybe reducing c-FLIP levels could help to improve bowel cancer treatment, by making them more susceptible to chemotherapy.

Before you get too excited, it’s important to stress that this work is still at an early stage. But there is some hope for the future. Small clinical trials involving RNAi for cancer treatment are currently in progress, suggesting a possible route to the clinic if all goes well.

Read the abstract of this paper

You can hear Professor Johnston talk about other aspects of his work in the April 2007 Cancer Research UK Podcast