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

Article

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.

Keywords

Apical polarity Tight junction Chromatin Cell nucleus Proliferation Cancer progression 

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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Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  1. 1.Department of Basic Medical Sciences and Purdue Center for Cancer ResearchPurdue UniversityWest LafayetteUSA

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