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Tissue Polarity-Dependent Control of Mammary Epithelial Homeostasis and Cancer Development: an Epigenetic Perspective

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Journal of Mammary Gland Biology and Neoplasia Aims and scope Submit manuscript

Abstract

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.

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Abbreviations

3D:

Three-dimensional

AJC:

Apical junctional complex

APC:

Adenomatous polyposis coli

Baz:

Bazooka

Dlg:

Discs-large

HDAC:

Histone deacetylase

HMG:

High mobility group

IDC:

Invasive ductal carcinoma

JAM:

Junctional adhesion molecule

Lgl:

Lethal giant larvae

MAGUK:

Membrane-associated guanylate kinase

MAPK:

Mitogen-activated protein kinase

MDCK:

Mardin-Darby Canine Kidney

SAF:

Scaffold-attachment factor

Scrib:

Scribble

std:

Stardust

ZO:

Zonula Occludens

ZONAB:

ZO-1 nucleic acid binding protein

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  1. Department of Basic Medical Sciences and Purdue Center for Cancer Research, Purdue University, 625 Harrison Street, Lynn Hall, West Lafayette, IN, 47907-2026, USA

    Sophie A. Lelièvre

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  1. Sophie A. Lelièvre
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Correspondence to Sophie A. Lelièvre.

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Support provided via the National Institutes of Health (NIH) (CA112017 and CA112613 to SAL) and the Susan G. Komen Breast Cancer Foundation (BCTR-0707641 to SAL).

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Lelièvre, S.A. Tissue Polarity-Dependent Control of Mammary Epithelial Homeostasis and Cancer Development: an Epigenetic Perspective. J Mammary Gland Biol Neoplasia 15, 49–63 (2010). https://doi.org/10.1007/s10911-010-9168-y

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  • DOI: https://doi.org/10.1007/s10911-010-9168-y

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