Researchers at Sweden's Karolinska Institutet have discovered a protein that inhibits the growth of breast tumors and has been related to a better prognosis in breast cancer patients.
The findings, which were published in the journal Nature Communications, could help researchers create novel treatments for difficult-to-treat kinds of breast cancer. Breast cancer affects roughly 10% of women at some point in their lives, and it is a significant medical and societal burden. ER-negative breast cancers, which lack estrogen receptors (ER) and consequently do not react to hormone therapy, have fewer treatment choices. Triple-negative breast tumors, which lack not only the ER but also the progesterone receptor and the HER2 receptor, are very difficult to treat.
“Identification of new molecular mechanisms that regulate the growth of ER-negative breast cancer is warranted, as these mechanisms may represent novel therapeutic targets,” says Per Uhlén, professor at Karolinska Institutet.
Professor Uhlén and colleagues discovered a novel way by which the ubiquitous protein GIT1 modulates Notch signalling, which affects the development and progression of ER-negative breast cancer. High levels of GIT1 blocked Notch signalling and protected against tumor growth in breast cancer cells, but low levels of GIT1 aided tumor growth. Patients’ ER-negative breast tumors had lower GIT1 levels than ER-positive breast tumors. The findings also revealed that patients with high levels of GIT1 in their ER-negative breast cancer have a better prognosis than those with low levels.
Notch signalling is a conserved cell-cell communication system that has been found to govern cell fate decisions in a variety of organs and stages of cell development. Overactive Notch signalling has previously been associated to a worse prognosis in breast cancer patients.
“Our results provide important information about a mechanism that controls the initiation and growth of breast tumours,” says Professor Uhlén. “We hope that these findings will inform the development of new therapies for patients with difficult-to-treat breast cancer“.
Uhlén’s research group is actively working in partnership with physicians treating patients with cancer to concentrate on research topics that are essential for the treatment of patients.
“We want to conduct research that can benefit patients with severe diseases,” says Professor Uhlén. “At Karolinska Institutet, we have state-of-the-art tools and equipment that can push the development of new therapies.”