SMAD4 and lung adenocarcinoma: We hypothesize that the following pathways might also be active in the PAECs and PASMCs of PH patients (129); In cultivated human lung adenocarcinoma cells STAT3 represses the transcription of SMAD3 in cooperation with SKI and SKIL preventing SMAD2, SMAD3, and SMAD4 from activating the transcription of SMAD3 (130) (Figure 3H).