Tumor Metastasis Promoters Identified

Scientists seeking to explain why cancer tumors metastasize have found that a transcription protein known as NFAT (nuclear factor of activated T cells) is a target of signals from á6â4 integrin, which has been linked with several features of metastatic tumors, including epithelial cell motility, cellular survival, and carcinoma invasion. The study was published June 24, 2002, in the on-line issue of Nature Cell Biology.

In order for a tumor to metastasize, certain genes have to be activated to produce enzymes necessary to invade blood vessel walls and penetrate other tissues. While looking for activators of these genes, researchers from Harvard Medical School (Boston, MA, USA) found high levels of NFAT in certain types of cancer cells.

Because there was no information indicating NFAT expression in human metastatic cancer, the researchers evaluated the presence of NFAT in tissue samples from five breast cancer patients with aggressive grade III ductal carcinoma, who had positive lymph node metastases at the time of diagnosis. Besides showing a high correlation between tumor aggression and NFAT levels, the researchers showed that NFAT is found in association with another protein, á6â4 integrin. This integrin has been linked with several traits of metastatic tumors, including epithelial cell motility, cellular survival, and carcinoma invasion.

"Cancer has been attacked from a large number of fronts, but this discovery presents a previously unappreciated role for NFAT in human cancer,” said Dr. Alex Toker, department of pathology at Harvard and senior author. "If we pursue this avenue and add NFAT to the growing list of proteins that have been shown to be important for disease progression, we could be offering a novel target for drug discovery to block this aspect of cancer progression. We may be providing another weapon in our arsenal in the fight against cancer.”