Seventh Framework Programme - European Union
An EU consortium to identify novel targets and drugs for cancer treatment

Flies and fate

By Brona McVittie

Sarah Palin might be a little surprised to learn that she has thousands of genes in common with the fruit fly (watch video). Yet for this very reason flies are key to understanding many human diseases. For more than a century scientists have been using Drosophila melanogaster as a tool to better understand biological development. This work has fuelled many major breakthroughs in the treatment of human diseases including cancer.

“Although the public is often amazed that we use insects to try and understand human cancer,” says Maria Dominguez (Institute for Neurosciences, Alicante, Spain), “Drosophila is like the Rosetta Stone that helps us to understand the language of different genomes. A simple genome (fly) can teach us a lot about complex genomes (humans).”

Fly-biologist, Buzz Baum (Laboratory of Molecular Cell Biology, UCL, UK) elucidates; “A gene called Lethal giant larvae (Lgl) was discovered through genetic screens on flies in the seventies. No one had yet found a gene that quashed the growth of tumours in any animal. Flies born with mutations in Lgl get bigger and bigger and then die because of unregulated cell growth. Human versions of this and other tumour-suppressor genes play a role in cancer.”

Do flies get cancer? “Flies only live for a few weeks so they don’t have to maintain tissues like we do over long periods. It’s the rapidly dividing tissues that are prone to cancers; the more cells we make, the greater the likelihood of a mutation during our lifetime, the greater the likelihood of mutations that lead to cancer. So, although flies can get cancer, they rarely do in nature.”

So how do mutations in fly Lgl lead to cancer? “Curiously, fly tumour-suppressor genes like Lgl don’t directly control cell growth, division or death, the usual suspects we think about when considering cancer. Instead Lgl controls cell polarity. This is one of the most basic properties of normal cells. Cell polarity determines, which is the top and which the bottom of a cell. This is the first thing to go wrong when Lgl is lost,“ confirms Buzz.

“Why is cell polarity so important for the prevention of cancer? Cells in healthy tissue must be polarised in order to communicate properly; so that each cell grows and divides on schedule. On the other hand, tumours are ugly, disorganised clumps of cells confused about their polarity and unable to understand each other. Losing normal cell controls can lead to unregulated tissue overgrowth and cancer.”