Drug Could Be Developed to Prevent Tumor Growth

Scientists have found two proteins that work together to promote the spread of breast cancer, as well as a method that stops tumor cells from forming, according to a new study.

The finding, which appears in the June 2004 issue of the journal Cancer Cell, might one day lead to drugs that could trigger the death of breast cancer cells, says Rakesh Kumar, Ph.D., professor of cellular and molecular oncology and lead investigator on the study at M. D. Anderson. However, much more study needs to be done, he cautions.

Proteins modify chemicals

The proteins, Pak1 and DLC1 (dynein light chain 1), normally help cells move from place to place and are made in large quantities in breast cancer cells. Researchers discovered that when the two proteins interact, Pak1 chemically modifies DLC1 at a single site.

As a result, the cells:
- No longer respond to death signals
- Continue to survive, multiply and spread 

When the scientists looked for DLC1 in breast cancer tumors, they found:

- 54 out of 60 had elevated levels of DLC1
- Five out of six tumor samples studied had increased levels of the modified DLC1 that does not respond to cell death signals 

Scientists also found cells with increased levels of DLC 1 also formed tumors in animals, and that such cells:

- Moved faster than normal cells
- Reproduced faster
- Grew without normal cell contacts, which is called anchorage independence

Taken together, these studies show cells that increased levels of DLC1 have all of the characteristics required for successful tumor formation, Kumar says.

Modification prevents cancer cells

But when the research team engineered a form of the DLC1 protein missing the crucial modification site, the protein could no longer block cell death signals and cells containing the modified version of DLC1 could no longer form tumors in mice.

Kumar says that since DLC1 is a small protein and the research team has identified exactly how it becomes modified by Pak1, it may be possible in the future to design drugs to inhibit its activity. Such inhibitors might restore the cell’s normal recognition of cell death signals, Kumar says.

However, he adds, more work needs to be done to understand how and why increased levels of DLC1 contribute to the development of breast cancer, and perhaps, other tumor types.