Figure 8.

Crosstalk between KLF4 and TGF-β signaling plays an important role in CE homeostasis. In homeostatic condition, KLF4 controls cell proliferation by regulating proper cellular levels of SMAD7, p16, and p27. SMAD7 inhibits TGF-β signaling cascade suppressing EMT, whereas p16 and p27 regulate cell cycle progression. Decreased levels of KLF4 result in downregulation of SMAD7, which in turn leads to activation of TGF-β signaling and EMT, as well as downregulation of p16 and p27 that leads to dysregulated cell cycle progression through the G1/S phase.