Inflammation-Mediated Genetic and Epigenetic Alterations Drive Cancer Development in the Neighboring Epithelium upon Stromal Abrogation of TGF-β Signaling
Figure 7
Schematic hypothesis for the development of forestomach SCC due to loss of Tgfbr2 in stromal fibroblasts.
(A) Tgfbr2 deletion in FSP1+ fibroblasts results in inflammation and infiltration of CD45+ cells in the microenvironment; (B) Inflammation induces DNA damage characterized by 8-oxo-dG and H2AX production in epithelia; (C) epigenetic silencing of p21 and p16, and genetic loss of p15 and p16 in epithelia; (D) loss of cell cycle control and hyper-proliferation of epithelia, development of SCC.