Yi-Arial Zeng

Shanghai Institutes for Biological Sciences, CAS


Wnt Signaling and Protein C Receptor in Regulating Mammary Stem Cells and Breast Cancer


The mammary gland is composed of multiple types of epithelial cells that are generated by mammary stem cells (MaSCs) residing at the top of the hierarchy. The identity of MaSCs was unclear. Our study demonstrates that Procr (Protein C receptor), a novel Wnt-target in the mammary gland, marks a population of multipotent MaSC. Procr-expressing cells display high regenerative capacity in transplantation assays and differentiate into all lineages of the mammary epithelium by lineage tracing. In mouse, Procr was required for the mammary development and homeostasis, and was important for the initiation of mammary tumor. Triple-negative breast cancer (TNBC) is a highly aggressive malignancy with no targeted treatment option. We found that PROCR is highly expressed in TNBC patient samples, and associated with poor prognosis. Remarkably, targeting PROCR by a neutralizing antibody inhibits TNBC tumor growth. PROCR represents a surface therapeutic target for human TNBC.


Dr. Arial Zeng is the professor in the Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences. Her research focuses on the following questions: 1) What is the mechanism through which Wnt signals maintain the stem cell multipotent state? 2) How do the stem cells and their niche interact? 3) What is complete lineage of mammary development? The long-term goal of Professor Zeng’s lab is to determine how the stem and progenitor cell regulatory mechanisms have deviated in breast cancer, and to learn how to control the players in these machineries for the purposes of regenerative and cancer medicine.