An in vivo RNAi screen identifies SALL1 as a tumor suppressor in human breast cancer with a role in CDH1 regulation

J. Wolf, K. Müller-Decker, C. Flechtenmacher, F. Zhang, M. Shahmoradgoli, G. B. Mills, J. D. Hoheisel, M. Boettcher

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)4273-4278
Number of pages6
JournalOncogene
Volume33
Issue number33
DOIs
StatePublished - Aug 14 2014
Externally publishedYes

Keywords

  • CDH1
  • EMT
  • In vivo RNAi screening
  • SALL1
  • shRNA screen
  • tumor suppressor

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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