The overexpression of the putative gut stem cell marker Musashi-1 induces tumorigenesis through Wnt and Notch activation

Amelie Rezza, Seham Skah, Colette Roche, Julien Nadjar, Jacques Samarut, Michelina Plateroti

Research output: Contribution to journalArticlepeer-review

103 Scopus citations

Abstract

The RNA-binding protein Musashi-1 (Msi1) has been proposed as a marker of intestinal epithelial stem cells. These cells are responsible for the continuous renewal of the intestinal epithelium. Although the function of Msi1 has been studied in several organs from different species and in mammalian cell lines, its function and molecular regulation in mouse intestinal epithelium progenitor cells are still undefined. We describe here that, in these cells, the expression of Msi1 is regulated by the canonical Wnt pathway, through a mechanism involving a functional Tcf/Lef binding site on its promoter. An in vitro study in intestinal epithelium primary cultures showed that Msi1 overexpression promotes progenitor proliferation and activates Wnt and Notch pathways. Moreover, Msi1-overexpressing cells exhibit tumorigenic properties in xenograft experiments. These data point to a positive feedback loop between Msi1 and Wnt in intestinal epithelial progenitors. They also suggest that Msi1 has oncogenic properties in these cells, probably through induction of both the Wnt and Notch pathways.

Original languageEnglish
Pages (from-to)3256-3265
Number of pages10
JournalJournal of Cell Science
Volume123
Issue number19
DOIs
StatePublished - 1 Oct 2010
Externally publishedYes

Keywords

  • Intestinal epithelium, intestinal tumorigenesis
  • Musashi-1
  • Stem cells
  • Wnt

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