ARRDC3 suppresses colorectal cancer progression through destabilizing the oncoprotein YAP

Although colorectal cancer ( CRC ) is a prevalent malignancy of the digestive system, the underlying mechanisms of CRC tumorigenesis are still elusive. Arrestin‐related domain‐containing protein‐3 ( ARRDC 3) has been reported to promote lysosome‐mediated protein degradation. In the present study, we find that the expression of ARRDC 3 is downregulated in CRC specimens. Mechanistically, we reveal that ARRDC 3 binds and decreases expression of the oncoprotein YAP , the cotranscription factor of the Hippo pathway. The regulation of the Hippo pathway by ARRDC 3 is conserved from Drosophila to mammals. Furthermore, we demonstrate that ARRDC 3 plays an anti‐oncogenic role in CRC progression by promoting YAP degradation. Finally, we show that ARRDC 3 increases the sensitivity of CRC cells toward chemotherapeutic drugs. Taken together, our findings point to ARRDC 3 as a potential target for CRC treatment.