While the explanation as to how loss of smad2 paradoxically reduces tumor growth in 4T1 cell is currently not clear, it is likely that the impairment of p53 tumor suppressive response in 4T1 cell (p53 null), which has been shown to be required for TGF-β-mediated tumor suppressive mechanism, may partly contribute to this unique phenomenon32. Here, SMAD2 is linked to neoplasm.