SMAD3 and lung cancer: One aspect of such epigenetic control is the regulation of TGFβ signaling components such as the Smad2 and Smad3 genes, whose expression is negatively regulated by HDAC1; during lung cancer cell EMT, profilin-2 directly binds to HDAC1 and sequesters it from its nuclear–chromatin targets, resulting in the upregulation of Smad2 and Smad3, which can then contribute to the EMT response [205].