AMOT is required for YAP function in high glucose induced liver malignancy.

AMOT has been identified as a YAP interactor. However, how AMOT regulates YAP remains unclear and controversy. Here, we identified that besides YAP, AMOT was another Hippo signaling core factor which could be O-GlcNAcylated. Moreover, high glucose (HG) was able to enhance the expression and O-GlcNAcylation of AMOT. We also found that HG stimulated nuclear accumulation, transcription activity, interaction with transcription factor and transcription of target genes of YAP via AMOT, while AMOT acted as a suppressor of YAP in normal glucose level. Finally, we observed the upregulation and nuclear accumulation of AMOT and YAP in Streptozocin (STZ) induced high glucose mice. Collectively, we have uncovered that AMOT acts as a YAP stimulator in high glucose level. Targeting the aberrantly regulated core factors in Hippo pathway might be a more effective therapeutic approach for liver cancer associated with possibly diabetes.