SLUG: Critical regulator of epithelial cell identity in breast development and cancer

Cell Adh Migr. 2014;8(6):578-87. doi: 10.4161/19336918.2014.972740.

Abstract

SLUG, a member of the SNAIL family of transcriptional repressors, is known to play a diverse number of roles in the cell, and its deregulation has been observed in a variety of cancers including breast. Here, we focus on SLUG's role as a master regulator of mammary epithelial cell (MEC) fate and lineage commitment in the normal mammary gland, and discuss how aberrant SLUG expression can influence breast tumor formation, phenotype, and progression. Specifically, we discuss SLUG's involvement in MEC differentiation, stemness, cellular plasticity, and the epithelial to mesenchymal transition (EMT), and highlight the complex connection between these programs during development and disease progression. Undoubtedly, delineating how molecular factors influence lineage identity and cell-state dynamics in the normal mammary gland will contribute to our understanding of breast tumor heterogeneity.

Keywords: BCSC, Breast Cancer Stem Cell; BM, Basement Membrane; BRCA1, Breast Cancer Associated 1; CK, Cytokeratin; CSC, Cancer Stem Cell; E-CAD, E-Cadherin; EMT; EMT, Epithelial to Mesenchymal Transition; ERα, Estrogen Receptor; HDAC, Histone Deacetylasae; HMECs, Human Mammary Epithelial Cells; IHC, Immunohistochemical; LSD1, Lysine Specific Demethylase 1.; ME, Myoepithelial; MEC, Mammary Epithelial Cell; MaSC, Mammary Stem Cell; SLUG; SMA, Smooth Muscle Actin; SNAG, Snai.Gfi-1; WT, Wild type; breast cancer; cellular plasticity; differentiation; mammary stem cells.

Publication types

  • Review

MeSH terms

  • Animals
  • Breast / cytology*
  • Breast / embryology
  • Breast / growth & development*
  • Breast Neoplasms / etiology*
  • Breast Neoplasms / genetics
  • Breast Neoplasms / physiopathology
  • Cell Differentiation
  • Cell Line, Tumor
  • Cell Lineage / physiology*
  • Disease Progression
  • Epithelial Cells / cytology*
  • Epithelial Cells / physiology
  • Epithelial-Mesenchymal Transition / physiology
  • Female
  • Humans
  • Snail Family Transcription Factors
  • Transcription Factors / metabolism*

Substances

  • SNAI1 protein, human
  • Snail Family Transcription Factors
  • Transcription Factors