Cytokeratin 5 determines maturation of the mammary myoepithelium

Summary At invasion, transformed mammary epithelial cells expand into the stroma through a disrupted myoepithelial (ME) cell layer and basement membrane (BM). The intact ME cell layer has thus been suggested to act as a barrier against invasion. Here, we investigate the mechanisms behind the disruption of ME cell layer. We show that the expression of basal/ME proteins CK5, CK14, and α-SMA altered along increasing grade of malignancy, and their loss affected the maintenance of organotypic 3D mammary architecture. Furthermore, our data suggests that loss of CK5 prior to invasive stage causes decreased levels of Zinc finger protein SNAI2 (SLUG), a key regulator of the mammary epithelial cell lineage determination. Consequently, a differentiation bias toward luminal epithelial cell type was detected with loss of mature, α-SMA-expressing ME cells and reduced deposition of basement membrane protein laminin-5. Therefore, our data discloses the central role of CK5 in mammary epithelial differentiation and maintenance of normal ME layer.
Graphical abstract
Highlights • Cytokeratin 5 (CK5) impacts mammary epithelial cell lineage differentiation • CK5 loss at pre-invasive stage causes impaired maturation of myoepithelial cells • CK5 loss causes SLUG downregulation and differentiation bias in mammary progenitors
Cell Biology; Developmental Biology; Biophysics