Interestingly, although it is generally accepted that Hakai mediated E-cadherin ubiquitination for proteasomal degradation [10–12], a recent study demonstrated that CD147 overexpression in HCC cells enhances E-cadherin ubiquitination by recruiting Hakai for lysosomal degradation, which is prevented by chloroquine (an inhibitor of lysosomal degradation) treatment, but not MG132 [38]. The gene discussed is CBLL1; the disease is hepatocellular carcinoma.