SMAD3 and cancer: It has been found that Rif1 depletion can sensitize cancer cells to drug treatment with enhanced apoptosis.51 Recent study revealed that Rif1 is important in maintaining the telomere stability in ESCs as it can repress Zscan4, which can trigger hyper-telomere elongation and cell senescence from an elevated expression.18 Interestingly, the Rif1 shRNA-transduced Smad3−/− ESCs formed smaller teratomas than WT and Smad3−/− ESCs.