The Induction of Selected Wnt Target Genes by Tcf1 Mediates Generation of Tumorigenic Colon Stem Cells

Publication date: 2 May 2017
Source:Cell Reports, Volume 19, Issue 5
Author(s): Daisuke Shiokawa, Ai Sato, Hirokazu Ohata, Michihiro Mutoh, Shigeki Sekine, Mamoru Kato, Tatsuhiro Shibata, Hitoshi Nakagama, Koji Okamoto
The generation of tumor-initiating cells during colon carcinogenesis is associated with the dysregulation of Wnt signaling, which is known to act on Lgr5-positive intestinal stem cells. Here, using single-cell qPCR analysis, we identified a subset of Lgr5-positive stem cells that emerged during tumorigenesis in a mouse model of colon cancer. These tumor-specific Lgr5-positive cells expressed low levels of Ceacam1 and increased levels of a specific subset of Wnt targets and showed enhanced tumorigenicity. Among the Wnt targets that were specifically expressed, the long isoform of Tcf1 was required for the proliferation of tumor organoids and drove a unique Wnt target gene expression profile. Tcf1 expression increased at an early stage of colon carcinogenesis and was associated with the nuclear accumulation of β-catenin, underscoring the importance of the induction of Tcf1 expression in generating tumorigenic colon stem cells.

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Teaser

Shiokawa et al. show that a tumorigenic subpopulation of Lgr5-positve cells emerges during colon tumorigenesis. The tumorigenic Lgr5-positive cells express a distinct subset of Wnt target genes. The long isoform of Tcf1 dictates the unique expression profile of the Wnt targets and mediates generation of colon tumorigenic stem cells.


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