This delicate tumor-suppressing homeostatic balance is upset in a wide spectrum of human cancers due to mutations, deletions, epigenetic alterations or expression variability in key elements including TGF-βRI and II, SMAD 2, 3 and 4 as well as TGF-β1 itself resulting in the transition of TGF-β1 from an anti- to pro-tumorigenic cytokine [22,28,29,30]. The gene discussed is TGFB1; the disease is cancer.