SMAD7 and neoplasm: To reconcile these paradoxical observations, we noted that TGFβ signaling operates in a negative feedback loop mediated by the inhibitory Smad, Smad7,28, 29 which is upregulated by TGFβ via the pro-inflammatory transcription factor NFκB.30, 31 Oxidative stress is also strongly associated with NFκB activation.32, 33 Hence, FIBs exposed to H2O2 are initially responsive to TGFβ, which facilitates their activation by tumor epithelia- and CAF-derived TGFβ.