Distinct from Smurf1-mediated proteolytic degradation of RUNX2, it has been demonstrated that cyclin D1/Cdk4 complex phosphorylates RUNX2 and promotes its degradation in an ubiquitin/proteasome-dependent manner.52 In addition, several lines of evidence suggest that Smurf1 has a pro-oncogenic potential.53, 54 In a good agreement with this notion, Shain et al.55 described that Smurf1 gene is amplified in certain subset of human pancreatic cancers and might contribute to their invasiveness. This evidence concerns the gene RUNX2 and familial pancreatic carcinoma.