Wnt/β-catenin controls stem cells in regeneration and tumor formation
Walter Birchmeier1, Peter Wend1, Christoph Loddenkemper2 & Ulrike Ziebold1
Our laboratory works on Wnt/β-catenin signaling in precursor and stem cells of various organs. The data show that Wnt/β-catenin controls cell lineage specification in embryogenesis and organogenesis. General interest sparked anew by recent evidence suggesting that organ as well as cancer stem cells share core signaling and transcriptional modules. We used genetic mouse models to study the necessity of Wnt/β-catenin signaling in stem cells of the salivary gland. Remarkably, the combined activation of Wnt/β-catenin and blocked Bmp signals produced highly aggressive squamous cell carcinomas. These tumors contained a high number of CD24+CD29+ stem cells, and as few as 500 of these cells induced tumors following transplantation into NOD/SCID mice. If the Wnt/β-catenin and Bmp pathways were individually mutated, stem cells showed an increased potential for tissue regeneration but no tumors ensued. The switch from organ stem cells to cancer stem cells involves a global increase in histone 3K4 methylation and a decrease of H3K27 methylation. Our work thus defines a switch in stem cell potency from single to double mutations. Human squamous cell carcinomas are also characterized by activated Wnt/β-catenin and suppressed Bmp signaling.