OTUD1 first prevents the degradation of SMAD7 by cleaving its K48-type poly Ub chain and then promotes the formation of SMAD7/Smurf2 complex by cleaving its K33-type poly Ub chain, thus antagonizing the TGF-β/TβRI/SMAD signaling pathway, ultimately inhibiting EMT and cancer stem cell properties in breast cancer. Here, OTUD1 is linked to cancer.