Tissue polarity-dependent control of mammary epithelial homeostasis and cancer development: an epigenetic perspective.

The basoapical organization of monolayered epithelia is defined by the presence of hemidesmosomes at the basal cellular pole, where the cell makes contacts with the basement membrane, and tight junctions at the opposite apical pole. In the mammary gland, tight junctions seal cell-cell contacts against the lumen and separate the apical and basolateral cell membranes. This separation is critical to organize intracellular signaling pathways and the cytoskeleton. The study of the impact of the highly organized apical pole, and notably apical polarity regulators (Crb complex, Par complex, and Scrib, Dlg, Lgl proteins) and tight junction proteins on cell phenotype and gene expression has revealed an intricate relationship between apical polarity and the cell nucleus. The goal of this review is to highlight the role of the apical pole of the tissue polarity axis in the epigenetic control of tissue phenotype. The organization of the apical pole and its importance in mammary homeostasis and tumorigenesis will be emphasized before presenting how apical polarity proteins impact gene expression indirectly, by influencing signal transduction and the location of transcription regulators, and directly, by participating in chromatin-associated complexes. The relationship between apical polarity and cell nucleus organizations might explain how apical polarity proteins could switch from nuclear repressors to nuclear promoters of cancerous behavior following alterations in the apical pole. The impact of apical polarity proteins on epigenetic mechanisms of gene expression will be discussed in light of increased evidence supporting a role for apical polarity in the fate of breast neoplasms.