See What HealthDay Can Do For You
Contact Us

Gene Implicated in Cancer's Spread

NFAT unusually active in some metastatic tumors

WEDNESDAY, June 26, 2002 (HealthDayNews) -- Many cancers spread, striking off from the main tumor to take up in distant organs. However, the mechanics behind this migration aren't well understood.

Now, a new study has found a gene in breast cancer cells that might help explain the phenomenon. The gene, called NFAT, regulates a variety of body functions, from the immune system to vessel formation. And it may give breast cancer cells a compass with which they can navigate their migration. A report on the findings appears this week in Nature Cell Biology.

NFAT (short for nuclear factor of activated T-cells) is an umbrella acronym for a group of genes that turn on other genes. Discovered about two decades ago as a puppeteer in the immune system -- and subsequently, in many other systems -- NFAT is the target of the transplant drug cyclosporine, which suppresses the immune response against grafted organs.

More recently, scientists found chemicals that block NFAT have anti-tumor properties, hinting at a role for the regulatory molecule in the spread of cancer.

In the new work, researchers led by Sebastien Jauliac, a postdoctoral fellow at Harvard University's Beth Israel Deaconess Medical Center in Boston, looked for NFAT activity in invasive breast and colorectal cancer carcinoma cells growing in lab dishes. Carcinomas account for about 70 percent to 80 percent of all human cancers.

Both NFAT1 and a newly identified form of the protein, NFAT5, were present in the tumor cells and appeared to help promote invasiveness.

Jauliac's team then looked for and found strong NFAT signals in tissue samples taken from five women with aggressive breast cancer that had spread to their lymph glands. They showed that NFAT activity was linked to that of another gene, alpha 6 beta 4 integrin, known to be involved in cancer cell migration.

Integrin may activate NFAT, which in turn triggers gene changes that send tumor cells wandering, explains Alex Toker, a Harvard pathologist who headed the research effort.

Once activated, carcinoma cells can move away from the main tumor, burrow through nearby blood vessel membranes, and break out into the circulatory system, where they have open access to the rest of the body.

Although the researchers looked only at breast and colon carcinomas, Toker says he has a "strong feeling" that NFAT activity will be present in virtually all other carcinomas.

It's still unclear how NFAT might trigger metastasis. Jauliac says the gene might switch on instructions within tumors that lead them to behave like immune cells. "Immune cells have the property of migrating when there's an infection," he explains.

However, Dr. Gerald Crabtree, the Stanford University biochemist who discovered NFAT, says it's "a bit early" to draw any conclusions from the latest findings. "What is lacking is the evidence in patients with cancer of mutations" in NFAT that might alter its normal functioning, says Crabtree, who reviewed the paper for the journal.

If NFAT errors ultimately prove to have metastatic powers, Crabtree says, they're not likely to stem from its role in the immune system. Rather, the gene's influence over blood vessel formation is a more probable prospect.

Whatever the case, NFAT may make a promising target for new tumor drugs. However, these might be long in coming. Cyclosporine, which is known to inhibit NFAT in normal cells, has no sway over it in cancerous tissue, Jauliac says.

What To Do

For more on cancer, try the American Cancer Society or the National Cancer Institute.

SOURCES: Alex Toker, Ph.D., assistant professor, pathology, Harvard Medical School, Boston; Sebastien Jauliac, Ph.D., postdoctoral fellow, Harvard University, Boston; Gerald Crabtree, M.D., professor, pathology and developmental biology, Stanford University School of Medicine, Stanford, Calif., and investigator, Howard Hughes Medical Institute, Chevy Chase, Md.; June 24, 2002, Nature Cell Biology
Consumer News


HealthDay is the world’s largest syndicator of health news and content, and providers of custom health/medical content.

Consumer Health News

A health news feed, reviewing the latest and most topical health stories.

Professional News

A news feed for Health Care Professionals (HCPs), reviewing latest medical research and approvals.