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Tissue repair and stem cell renewal in carcinogenesis

Abstract

Cancer is increasingly being viewed as a stem cell disease, both in its propagation by a minority of cells with stem-cell-like properties and in its possible derivation from normal tissue stem cells. But stem cell activity is tightly controlled, raising the question of how normal regulation might be subverted in carcinogenesis. The long-known association between cancer and chronic tissue injury, and the more recently appreciated roles of Hedgehog and Wnt signalling pathways in tissue regeneration, stem cell renewal and cancer growth together suggest that carcinogenesis proceeds by misappropriating homeostatic mechanisms that govern tissue repair and stem cell self-renewal.

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Figure 1: Hh and Wnt signalling pathways.
Figure 2: Model for carcinogenesis resulting from persistence of a state of injury repair.
Figure 3: Increased cancer risk during chronic injury.

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Acknowledgements

We thank E. Matunis for comments on the manuscript. Work in our laboratories is supported by the Howard Hughes Medical Institute, NIH, the Prostate Cancer Foundation and the Flight Attendant's Medical Research Institute. We apologise to authors of original work who could only be indirectly cited because of editorial constraints.

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Under a licensing agreement between Curis, Inc. and the Johns Hopkins University, P. A. B. and the University hold equity in Curis and are entitled to a share of royalties from sales of the products described in this article. P. A. B. and D. M. B. also receive payment and/or equity for service as consultants to Curis, Inc. and Genentech Inc. The terms of this arrangement are being managed by the Johns Hopkins University in accordance with its conflict of interest policies.

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Beachy, P., Karhadkar, S. & Berman, D. Tissue repair and stem cell renewal in carcinogenesis. Nature 432, 324–331 (2004). https://doi.org/10.1038/nature03100

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