Sal-like 4 (SALL4) Suppresses CDH1 Expression and Maintains Cell Dispersion in Basal-Like Breast Cancer

FEBS Lett. 2013 Sep 17;587(18):3115-21. doi: 10.1016/j.febslet.2013.07.049. Epub 2013 Aug 14.

Abstract

In cell cultures, the dispersed phenotype is indicative of the migratory ability. Here we characterized Sal-like 4 (SALL4) as a dispersion factor in basal-like breast cancer. Our shRNA-mediated SALL4 knockdown system and SALL4 overexpression system revealed that SALL4 suppresses the expression of adhesion gene CDH1, and positively regulates the CDH1 suppressor ZEB1. Cell behavior analyses showed that SALL4 suppresses intercellular adhesion and maintains cell motility after cell-cell interaction and cell division, which results in the dispersed phenotype. Our findings indicate that SALL4 functions to suppress CDH1 expression and to maintain cell dispersion in basal-like breast cancer.

Keywords: Adhesion; Basal-like breast cancer; E-cadherin; EMT; Epithelial mesenchymal transition; HMLE; Migration; SALL4; Sal-like 4; Transcription factor; epithelial mesenchymal transition; immortalized human mammary epithelial cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, CD
  • Cadherins / genetics*
  • Cadherins / metabolism
  • Cell Communication
  • Cell Count
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Genes, Reporter
  • Homeodomain Proteins / genetics*
  • Homeodomain Proteins / metabolism
  • Humans
  • Luciferases
  • Neoplasms, Basal Cell / genetics*
  • Neoplasms, Basal Cell / metabolism
  • Neoplasms, Basal Cell / pathology
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism
  • Signal Transduction
  • Transcription Factors / antagonists & inhibitors
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism
  • Zinc Finger E-box-Binding Homeobox 1

Substances

  • Antigens, CD
  • CDH1 protein, human
  • Cadherins
  • Homeodomain Proteins
  • RNA, Small Interfering
  • SALL4 protein, human
  • Transcription Factors
  • ZEB1 protein, human
  • Zinc Finger E-box-Binding Homeobox 1
  • Luciferases