The gene, sometimes called "the guardian of the genome", has for some time been known to prevent genome mutation and cancer growth. However, new research has found a previously unknown mechanism of action of the gene, the suppression of the signals that cause cancer cells to move and spread through the body.
Several mutations must arise and collaborate within a single cell for cancer to develop. Single tumour-forming (oncogenic) mutations frequently induce multiple and contradictory signals that both promote and inhibit cancer proliferation. Mutations in the proteins Ras and p53 are implicated in the formation of colon, pancreas, lung and other cancers.
In the new research, published in the latest edition of 'Nature Structural and Molecular Biology', co-authors Dr Mingxuan Xia and Professor Hartmut Land, explored the involvement of the Rho family of proteins, in the progression from benign to malignant cancers. They found that the progression is controlled by the two well known cancer genes p53 and Ras.
"We have very little understanding of how Ras and p53 or any other potent gene mutations cooperate to cause malignant tumors," said Professor Land, chair of the Department of Biomedical Genetics and scientific director of the James P. Wilmot Cancer Centre at the University of Rochester Medical Centre.
"But we have suspected for a long time that the way to develop rational searches for new drug targets is to first understand how these oncogenes cooperate. And in this study we've shown for the first time that this idea might work."
A key event in the progression of cells to a malignant state during cancer progression is the abnormal acquisition of movement, which allows tumour cells to spread from their original location.
When the researchers activated Ras, they found that the factor Rho, a regulator of cell movement, moves to its functional site at the cell membrane, but is unable to trigger migration. If however, Ras is activated in the presence of a p53 mutation that decreases its activity, the membrane-localised Rho is activated allowing cell movement and the spread of malignant cancer.
This hitherto, unknown signalling mechanism may lead to Rho becoming an attractive target for the treatment of cancer, as it is highly active only in malignant cells.
"Now that we understand more about the role of Rho proteins as a target of cooperating cancer gene mutations in tumors with p53 mutations, we will look for other molecules with similar features," said Professor Land.
"Our hope is that this line of research will give us a range of novel opportunities for treatments of cancer patients. We are at the beginning of a new and exciting road."