Newly identified fly genes provide clue to tumour growth

Researchers from the Oxford University Department of Human Anatomy and Genetics have found a new class of genes that are critical for cell growth and may be involved in the uncontrolled growth that takes place in cancer. The discovery could provide a key to future tumour therapies.

The scientists made the discovery during investigations into the way in which cells respond to insulin to control their growth and metabolism. Studies first performed in the fruit fly have revealed that insulin and insulin-like molecules control the rate at which cells grow and subsequent work has revealed that many different types of tumour cell grow too rapidly because they are abnormally sensitive to these molecules. The sensitivity of cells to insulin is also controlled by levels of nutrients around the cell. Although molecules that transport nutrients into cells have been implicated in this process, until now it has not been clear which transporters might be involved.

The team turned again to the fly to address this question, using its powerful genetics to test several different types of nutrient transporter for effects on growth and insulin signalling. They found that one class of amino acid transporters, the proton-assisted transporters, whose functions were until now unclear, are uniquely able to enhance the cellular response to insulin and stimulate growth. Over-expression of these genes caused excessive growth in flies, whilst a mutation in one of the genes drastically reduced the flies’ growth. The researchers also found that one of these molecules acts in an unusual way – stimulating growth by sensing nutrients at the surface of the cell and not by bringing nutrients into the cell as expected.

The work, published in the latest edition of the journal Development,[http://dev.biologists.org/] is the result of a collaboration between two scientists from very different fields in the Department of Human Anatomy and Genetics, Dr Deborah Goberdhan and Dr David Meredith. Dr Goberdhan has pioneered the use of fruit flies to study the functions of human cancer genes, while Dr Meredith has characterised several other types of transport proteins in the past.

‘We are now testing whether the human equivalents of these genes act in the same way,’ explained Dr Goberdhan. ‘If they do, it may be possible to block their activity in cancer cells through drugs or by altering diet, and put a brake on tumour growth. Our work is not only helping us to understand growth regulation in normal development, but is providing new insights into the molecular processes underlying tumour formation and metabolic diseases such as diabetes.’

Since the most common form of diabetes is linked to changes in insulin sensitivity, the newly identified transporters may also be important in this disease, and Drs Goberdhan and Meredith are already working with human geneticists in Oxford to test whether these genes are affected in diabetic patients.