Grant: Project Grant

During pregnancy, the hormone prolactin (PRL) is essential for preparing the breast to produce milk. It guides breast cells to mature and stay functionally connected to ensure a mother can nourish her newborn. Beyond lactation, this maturation process acts as a natural defense; evidence shows that breastfeeding significantly lowers a woman's long-term risk of breast cancer. Cancer can arise when this maturation fails. Cells lose their specialized traits and revert to an aggressive, "immature" state, a shift called cellular plasticity. Our research shows that removing the prolactin receptor from mature breast cancer cells causes them to transform into an aggressive immature state resembling triple negative breast cancer cell type a particularly lethal form of breast cancer. This suggests that prolactin signaling is a natural safeguard that maintains breast cell maturity and suppresses cancer. We recently discovered that prolactin works by blocking a "growth switch" (the YAP-CCN2 pathway) that drives tumor spread. When prolactin is active, cells remain organized and resist turning into invasive cells capable of spreading to other organs. Clinical data support this: patients with higher prolactin receptor levels have better survival rates. Our project will map how prolactin orchestrates cell maturation at high resolution and test its ability to slow cancer in breast cancer patient-derived models. Finally, we will identify new molecular targets to develop therapies. By "re-teaching" aggressive cancer cells how to mature, we aim to develop innovative treatments that protect maternal health and reduce the burden of breast cancer for mothers and their families.