We report a novel functional antagonistic relationship between the prolactin (PRL)/prolactin receptor (PRLR) differentiation pathway and YAP-CCN2 oncogenic pathway in normal mammary epithelial cells and breast cancer cells that is essential for establishing/maintaining acinar morphogenesis, cell-cell junctions and the intracellular localization of apical-basal polarity protein complexes (Par, Crumb and Scrib). Here, CCN2 is linked to breast carcinoma.