Two proteins that normally help cells move from place to place and are made in large quantities in breast cancer cells work together to promote the survival and spread of breast cancer, according to a new study by scientists at The University of Texas M. D. Anderson Cancer Center.
The finding, which appears in the June 2004 issue of the journal Cancer Cell, links together for the first time two proteins known to influence cell shape and survival of cancer cells. What’s more, when the scientists created a single change in a small 19-amino acid portion of one of the proteins, it stopped tumor formation. The results may lead to new strategies to trigger cell death in cancer cells, the scientists say.
“We can now target these 19 amino acids,” says Rakesh Kumar, Ph.D., professor of cellular and molecular oncology and the study’s lead investigator. “We might be able to develop a small molecule, a drug that could target the business end of this protein to interfere with the transformation process.”
The National Cancer Institute estimates that nearly 13 percent, about 1 in 8, of all women in the United States will develop breast cancer. It is the most commonly diagnosed malignancy among women. The proteins that Kumar and his research team studied appear to be involved in the process of transforming normal breast cells into cancer cells in the majority of breast cancer cases.
The research team discovered that when the two proteins, Pak1 and DLC1 (dynein light chain 1) interact, Pak1 chemically modifies DLC1 at a single site and changes the cell’s ability to respond to cell death signals. When DLC1 is modified it interferes with the cell death signaling pathway. As a result, cells no longer respond to death signals and instead continue to survive, multiply and spread. The loss of ability to respond to cell death signals is a hallmark of cancer.
When the scientists looked for DLC1 in breast cancer tumors, they found 54 out of 60 had elevated levels of DLC1. When they examined some of the tumors in greater detail, they found five out of six tumor samples studied had increased levels of the modified DLC1 that does not respond to cell death signals.