An in Vivo RNAi Screen Identifies SALL1 as a Tumor Suppressor in Human Breast Cancer With a Role in CDH1 Regulation

Oncogene. 2014 Aug 14;33(33):4273-8. doi: 10.1038/onc.2013.515. Epub 2013 Dec 2.

Abstract

The gold standard for determining the tumorigenic potential of human cancer cells is a xenotransplantation into immunodeficient mice. Higher tumorigenicity of cells is associated with earlier tumor onset. Here, we used xenotransplantation to assess the tumorigenic potential of human breast cancer cells following RNA interference-mediated inhibition of over 5000 genes. We identify 16 candidate tumor suppressors, one of which is the zinc-finger transcription factor SALL1. Analyzing this particular molecule in more detail, we show that inhibition of SALL1 correlates with reduced levels of CDH1, an important contributor to epithelial-to-mesenchymal transition. Furthermore, SALL1 expression led to an increased migration and more than twice as many cells expressing a cancer stem cell signature. Also, SALL1 expression correlates with the survival of breast cancer patients. These findings cast new light on a gene that has previously been described to be relevant during embryogenesis, but not carcinogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / mortality
  • Breast Neoplasms / pathology
  • Cadherins / genetics
  • Cadherins / metabolism*
  • Carcinogenesis / metabolism
  • Cell Line, Tumor
  • Disease-Free Survival
  • Epithelial-Mesenchymal Transition
  • Female
  • Gene Expression
  • Gene Expression Regulation, Neoplastic
  • Gene Knockdown Techniques
  • Humans
  • Kaplan-Meier Estimate
  • Mice
  • Mice, Inbred NOD
  • Mice, SCID
  • Neoplasm Transplantation
  • Proportional Hazards Models
  • RNA Interference
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / metabolism*

Substances

  • Antigens, CD
  • CDH1 protein, human
  • Cadherins
  • SALL1 protein, human
  • Transcription Factors
  • Tumor Suppressor Proteins