SMAD3 and lung cancer: Importantly, recent demonstration of the pro-tumorigenic actions of S100A2 in lung cancer cells involving regulation of PI3K/Akt signaling and functional interaction with Smad3, which is enhanced in the presence of calcium and TGF-β and induces epithelial-mesenchymal transition (EMT) [20], further support our clinical findings of increased cytoplasmic and decreased nuclear S100A2 expression in OSCC.