Thus, Smad4-mediated signaling is required to initiate epithelial carcinogenesis subsequent to <i>TGFBR2</i> deletion in FSP1<sup>+</sup> fibroblasts.<b>Implications:</b> These findings reveal a complex cross-talk between epithelial cells and the stroma, wherein Smad4 is required to elicit squamous cell carcinomas in the forestomach of mice with <i>TGFBR2</i>-deficient stromal cells.<i></i>.
We show that the loss of both Cdh1 and Tgfbr2 in both models is sufficient to induce squamous cell carcinomas with animals succumbing to the invasive disease by 18 months of age.
We have previously observed that TGF-beta type II receptor (TbetaR-II) expression decreases in squamous cell carcinomas as tumors become less differentiated and more biologically aggressive.