Transforming Growth Factor β Superfamily Signaling in Development of Colorectal Cancer  Barbara Jung, Jonas J. Staudacher, Daniel Beauchamp  Gastroenterology  Volume 152, Issue 1, Pages 36-52 (January 2017) DOI: 10.1053/j.gastro.2016.10.015 Copyright © 2017 AGA Institute Terms and Conditions

Figure 1 TGF-β family member signaling and its target in CRC. Members of the TGF-β family are commonly mutated in CRCs. Various ligands bind to specific cell surface receptor systems to affect downstream SMAD and non-SMAD signaling. Pathway members commonly mutated in CRC are in green, members affected in other GI cancers are in purple, and members that have been found altered in both are striped. As depicted in this simplified cartoon, there is frequent cross-regulation among upstream and downstream pathway members that are context dependent. Gastroenterology 2017 152, 36-52DOI: (10.1053/j.gastro.2016.10.015) Copyright © 2017 AGA Institute Terms and Conditions

Figure 2 Epithelial-stromal signaling of TGF-β family members in normal colonic mucosa. In the differentiated normal intestinal cell crypt, various gradients of TGF-β family members maintain homeostasis. Importantly, while BMP appears to be secreted mostly by epithelial cells, fibroblasts are a significant source of TGF-β secretion. Gastroenterology 2017 152, 36-52DOI: (10.1053/j.gastro.2016.10.015) Copyright © 2017 AGA Institute Terms and Conditions

Figure 3 Epithelial-stromal signaling of TGF-β family members in CRC. In CRC, there is enhanced secretion of TGF-β family ligands by both stroma and epithelial cells leading to autocrine enhanced secretion, immune modulation, and EMT as well as fibroblast proliferation and tumor cell growth suppression. Gastroenterology 2017 152, 36-52DOI: (10.1053/j.gastro.2016.10.015) Copyright © 2017 AGA Institute Terms and Conditions