A set of intracellular signaling cascades referred to as the SMAD pathway are involved in controlling the proliferation and optimal maintenance of epithelial cells, which line body cavities. Ludwig Stanford researcher Michael Clarke and colleagues reported in Cell Stem Cell in July that a factor secreted by mammary stem cells, LEFTY1, inhibits SMAD2 and plays a central role in breast development and maintenance as well as in the genesis of certain breast cancers. LEFTY1, they found, is produced by mammary progenitor cells and drives proliferation of both normal and malignant mammary epithelial stem cells. The protein opposes an anti-proliferative signal transmitted to mammary stem cells by a protein named BMP7. Studies in xenografts of triple-negative breast cancer revealed that in breast cancer stem cells, LEFTY1 interacts with a protein named BMPR2—a transducer of the BMP7 signal—to drive cell proliferation. Such cells, it turns out, are highly dependent on LEFTY1 for proliferation. This suggests LEFTY1 might be a target for the development of drugs that disable cancer stem cells in triple-negative breast tumors, which remain notoriously difficult to treat.
This article appeared in the December 2020 issue of Ludwig Link. Click here to download a PDF (1 MB).