Study Sheds Light on Function of Protein Associated with High-Risk Breast Cancers

Photo of Josh CoonThe function of a protein associated with breast cancer development and metastasis is now better understood, based on a new study by University of Wisconsin Carbone Cancer Center (UWCCC) researchers.

The study identified how the protein, CARM1, recognizes its target proteins, and should lead to a better understanding of how the cancer develops as well as the discovery of targeted drug therapies.

“When CARM1 is overexpressed in breast cancer, the higher expression is correlated with a poorer prognosis,” said Dr. Wei Xu, professor of oncology at UWCCC and the McArdle Laboratory for Cancer Research. “But we know very little about how it works.”

CARM1 is a member of a related group of proteins known as PRMTs which all work by adding a small chemical modification, a methylation, to their target proteins, thus changing the function of the target. Previous work from Xu’s group has found a few cellular targets of CARM1, including one protein that promotes breast cancer metastasis when the protein has been chemically modified.

To understand how elevated CARM1 levels contribute to breast cancer growth, Xu wanted to know all its targets, not just a few. Then, she attended a UWCCC research meeting on campus, where both she and UWCCC member Dr. Joshua Coon, professor of biomolecular chemistry and chemistry, presented. Coon is also the Director of the NIH National Center for Quantitative Biology of Complex Systems, a Center housed at UW that specializes in protein identification techniques, including one known as quantitative mass spectrometry.

“After Wei presented, it became pretty clear that she had a problem that could benefit from our technology,” Coon said. “In the past, she could identify CARM1 targets, but it was one at a time. We can tell you all the proteins that are present in a sample, or, in her case, all the target proteins that are methylated by CARM1.”

Evgenia Shishkova, a graduate student who works with Coon through UW’s Integrated Program in Biochemistry, took on the project to identify all CARM1 targets in a highly efficient way. Rather than start with thousands of proteins and confirm or eliminate them one by one, she performed just two sets of experiments that isolated many new CARM1 targets.

To read more about this story, see the original release from the UW–Madison School of Medicine and Public Health.