‘U’ researchers identify molecule that causes rapid movement of cancer cells

By Mary Hannahan, Daily Staff Reporter
Published October 5, 2011

More than 40,000 Americans are projected to die of breast cancer this year, but researchers at the University’s Comprehensive Cancer Center are working on ways to decrease this number.

Sofia Merajver, professor of internal medicine and epidemiology and director of the University’s Center for Global Health, was the lead researcher of a study that identified the molecule that causes rapid movement of a cancer cell and the importance of disrupting the molecule to fight cancerous cells.

The molecule, called p38-gamma, controls the structure of the cytoskeleton of the cell and ultimately influences how the cell moves. A cancer cell’s cytoskeleton is typically arranged in bundles of fibers that make the cell move quickly. But the researchers discovered that deactivation of the p38- gamma molecule causes the fibers to be arranged like a basket weave, which interrupts the cell’s movement.

“What we were able to find is that the motion of the cell changed very drastically from being very fast, directed motion to being more like fluctuating back and forth without moving very great distances,” Merajver said. “The cells looked a little more like fried eggs or empanadas just sitting around versus the elongated cells that move large distances, which is the usual way aggressive cancer cells are.”

Merajver said the study is unique in that it provides understanding of the molecular basis for cell movement and identifies a target molecule that plays a specific role. She added the discoveries could lead to the development of new drugs to fight and prevent breast cancer by targeting cell motion.

“Hopefully we will be able to develop drugs against it,” Merajver said. “Whether it will be us here at the University of Michigan doing that or not, that remains to be seen — we’ll see what the future holds.”

The research also shows that analyzing live cells could be an effective way to monitor patients undergoing therapy. This would be done by obtaining cells from a patient and looking at them under a microscope while the cells are still alive, Merajver said. She added that live-cell monitoring is not widely used, but the study's findings suggest it would be a useful addition to certain cancer treatments.

“It could help to know if the therapy is working,” Merajver said. “One of the biggest problems in cancer is people may not be respondent to therapy, but that doesn’t mean that you know exactly where the cancer is. So we need to know indirectly sometimes if the cancer is being killed or not, or if it’s responding or not.”

According to Merajver, the Breast Cancer Research Foundation and the Avon Foundation have provided more than $2 million in funding for her team’s work over the last few years. She added that Breast Cancer Awareness Month plays an important role in furthering research to prevent the disease.

“Most of us feel that having this focus on breast cancer worldwide in October is extremely helpful to channel a lot of energy and funding to conquer breast cancer, because it’s a very complex disease that isn’t going to be a single solution,” Merajver said. “Breast Cancer Awareness Month puts scientists in touch with a lot a breast cancer survivors and advocacy groups, and they work together for one cause: to cure and prevent breast cancer.”

Researchers at the University’s Comprehensive Cancer Center were also awarded a $3.5 million grant from Susan G. Komen for the Cure in September to study cancerous stem cells and to develop and test new treatments for triple negative breast cancer — an aggressive form of the disease that disproportionately affects African-American women.

Max Wicha, the director of the Comprehensive Cancer Center and the principal investigator of the study, said research in this area will involve a collaboration between the Karmanos Cancer Institute in Detroit, the Van Andel Institute in Grand Rapids, Mich. and the Henry Ford Hospital. Since the centers are geographically diverse, treatments will be available to patients across the state, Wicha said.

After studying the differences in stem cells in the first phase of research, Wicha said he and the other researchers plan to develop medicine that can specifically target cancerous stem cells and develop therapies for triple negative breast cancer.

Wicha has previously studied why some cancers are more aggressive than others, and his research team has determined that the aggressiveness of the cancer depends on the amount of cancerous stem cells. Preliminary studies have shown that African-American women have more cancerous stem cells when they get breast cancer, while Caucasian women have the lowest percentage of stem cells when they have the disease, according Wicha.

“We really need to develop new therapies that are specific for this form of breast cancer and can offer women with this breast cancer a new hope,” Wicha said.