Researchers at MIT identify cancer gene

Researchers at the Massachusetts Institute of Technology, Cambridge, reported that they have identified a single gene that lends some cancer cells the ability to metastasize.

The discovery has led researchers to believe that, if they can pinpoint which genes are essential for invasion and metastasis, they can use that information for better diagnosis and therapy.

"I believe that invasion and metastasis are now ripe for a concerted attack because of two scientific advances: our deeper understanding of the molecular basis of cell adhesion based on the past couple of decades of cell biology and the availability of mammalian genomic sequences and methods for exploiting that information," said Richard O. Hynes, director of the Center for Cancer Research at MIT.

"These should allow a systematic search for alterations in genes controlling cell adhesion and migration, as well as other processes that underlie malignancy, and should provide a much deeper understanding of invasion and metastasis - the processes that really make cancer a killer disease," he said.

The guilty gene

To provide insight into the pattern of gene expression that allows tumors to metastasize, the researchers at MIT looked at variants of melanoma cells that were either likely or unlikely to metastasize.

Using new methods of DNA arrays to analyze the expression of multiple genes at a time, the researchers screened for the expression of around 10,000 genes (approximately 10% of the total number of human genes) and found 32 genes that increased in their expression in metastatic cells.

About half of those genes fall into three categories: genes affecting cell adhesion, genes affecting the cytoskeleton - the cell's internal framework - and potential regulators of angiogenesis (new blood vessel formation).

Of these, researchers selected rhoC, a regulator of cytoskeletal structure and cell movement that is regulated by cell adhesion and growth factor receptors, to test whether it played a central role in inducing metastasis.

"If we overexpress rhoC in poorly metastatic cells, they become highly metastatic. If we express an inhibitor of it in highly metastatic cells, then they show reduced metastasis," Hynes said.

RhoC was one of three genes that were expressed in all three metastatic melanoma cells from both the human and mouse lines that were studied. All three genes were somehow involved in the cell's cytoskeleton.

Said Hynes, "The altered expression of so many genes whose products regulate the actin cytoskeleton suggests an important role for cytoskeleton organization in tumor metastasis." PR