Adhesion in mammary development: novel roles for E-cadherin in individual and collective cell migration

Curr Top Dev Biol. 2015;112:353-82. doi: 10.1016/bs.ctdb.2014.12.001. Epub 2015 Feb 11.

Abstract

Epithelial tissues are essential for barrier function, secretion, and regulation of fluid transport. Their function requires cell polarity and cell-cell adhesion, mediated through intercellular junctions. Conversely, disruption of adhesion and polarity is thought to drive cancer progression. The mammary gland is an important model for cell adhesion due to its postnatal hormonally regulated development; ducts undergo branching morphogenesis in response to steroid hormones during puberty. These hormonal signals induce a transition from simple to stratified architecture, initiated by asymmetric luminal cell divisions. Ductal elongation is accomplished by this multilayered, low-polarity epithelium, and polarity is reestablished as elongation ceases. The requirement for cell adhesion has been tested in 3D culture and in vivo, using gene deletion, knockdown, and misexpression in both developmental and homeostatic contexts. Attention has focused on E-cadherin, the major classical cadherin in luminal epithelial cells. Classic studies revealed a requirement for E-cadherin during lactation, and E-cadherin loss is widely posited to promote metastasis. However, recent findings demonstrated a broader requirement for E-cadherin during branching morphogenesis and homeostasis and also, surprisingly, in epithelial dissemination. These studies suggest that long-standing models of the role of adhesion in epithelial biology need to be revisited. Advances in inducible gene expression and knockdown, CRISPR/Cas9 technology, and fluorescent labeling of genetically modified cells offer the opportunity to test the roles of diverse adhesion systems and to develop a mechanistic understanding of how cell adhesion regulates development and cancer.

Keywords: Branching morphogenesis; Breast cancer; Cadherin switch; E-cadherin; Epithelial–mesenchymal transition; Mammary epithelium; Metastasis; P-cadherin.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cadherins / metabolism*
  • Cell Adhesion / physiology*
  • Cell Movement / physiology*
  • Humans
  • Mammary Glands, Human / cytology*
  • Mammary Glands, Human / metabolism*
  • Organogenesis / physiology*
  • Signal Transduction

Substances

  • Cadherins