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Microenvironmental regulation of stem cells in intestinal homeostasis and cancer

Abstract

The identification of intestinal stem cells as well as their malignant counterparts, colon cancer stem cells, has undergone rapid development in recent years. Under physiological conditions, intestinal homeostasis is a carefully balanced and efficient interplay between stem cells, their progeny and the microenvironment. These interactions regulate the astonishingly rapid renewal of the intestinal epithelial layer, which consequently puts us at serious risk of developing cancer. Here we highlight the microenvironment-derived signals that regulate stem-cell fate and epithelial differentiation. As our understanding of normal intestinal crypt homeostasis grows, these developments may point towards new insights into the origin of cancer and the maintenance and regulation of cancer stem cells.

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Figure 1: Crypt homeostasis.
Figure 2: Stem cells and the environment in the adenoma–carcinoma sequence.
Figure 3: Regulatory signals of colon CSCs provide new therapeutic targets.

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Acknowledgements

We would like to thank the members of the laboratory and G. van den Brink for critically reading the manuscript. Our work is sponsored by grants from the Netherlands Organization for Scientific Research (NWO; VICI program) and from the Dutch Cancer Society (UVA2009-4416)

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Correspondence to Jan Paul Medema.

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Medema, J., Vermeulen, L. Microenvironmental regulation of stem cells in intestinal homeostasis and cancer. Nature 474, 318–326 (2011). https://doi.org/10.1038/nature10212

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