Research reveals possible cancer role for YAP gene

In collaboration with the Press Association

Researchers have identified a new role for a known gene, pointing to its possible involvement in the development of breast, liver and other types of cancer.

The team, based at the Harvard Medical School (HMS) and Massachusetts General Hospital, were looking in breast cancer cells for regions of DNA that had become duplicated, or 'amplified'.

"We screened the DNA from breast cancer cells for amplifications that are associated with tumour development," said lead author, Professor Daniel Haber.

They found an amplified region that contained a single gene, called YAP.

Scientists had previously studied YAP in fruit flies, and had found that it is part of a control mechanism known as the 'Hpo-Sav-Wts' pathway, that helps fruit fly cells to grow and survive ? key processes in the development of cancer.

But further studies in human cells grown in a Petri dish failed to find any conclusive role for YAP in human cancer.

Haber explained, "A similar region of DNA is also amplified in some human tumours, but this amplified region often contains other genes that are known to promote cell survival".

In the past, the idea that the YAP gene could play a role in these cancers had been largely ignored. "The amplified region we discovered excluded these other genes, which allowed us to focus on YAP as a new candidate," he added.

The new research used a novel technique to grow cancer cells in three-dimensional gels, allowing the cells to adopt an architecture similar to that found in the human breast.

Further work showed that high levels of YAP gene activity dramatically changed the way cells behaved, causing exactly the invasive behaviour associated with cancer.

"What we would like to understand next is how YAP is controlled by the Hpo-Sav-Wts pathway in human cells," said first author Michael Overholtzer.

The research is published in the Proceedings of the National Academy of Sciences.

Read the paper online (PDF)