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. 2016 Dec 8;7(12):e2515. doi: 10.1038/cddis.2016.408

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Copyright © 2016 The Author(s)

Cell Death and Disease is an open-access journal published by Nature Publishing Group. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

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Extrinsic and intrinsic effect of inflammatory-driven Notch activation on tumorigenesis. When Notch signaling is activated in macrophages, it can induce the production of specific inflammatory mediators which in turn stimulate epithelial cells: thus, although not occurring into the epithelial cell, the dysregulation of the Notch pathway can indirectly exert a control on tumor progression (extrinsic effect). Alternately, the inflammatory milieu can directly modulate the Notch signaling within the epithelial cells, regulating several molecular processes involved in tumorigenesis (intrinsic effect)