Moreover, SMAD2 downregulation or the loss of SMAD4 diminishes TGF-β-dependent expression of tumor suppressor genes, leading to the upregulation of anti-apoptotic proteins BCL2 and BCLw, corresponding to resistance development of NSCLC cells and CRC cells to platinum anti-cancer compounds and 5-fluorouracil, respectively [128, 130]. The gene discussed is SMAD4; the disease is cancer.