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 (ARRDC3) has been reported to promote lysosome‐mediated protein degradation. In the present study, we fin...

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Bibliographic Details
Published in:FEBS letters 2018-02, Vol.592 (4), p.599-609
Main Authors: Shen, Xu, Sun, Xiaohan, Sun, Bing, Li, Tao, Wu, Guoliang, Li, Yuantao, Chen, Lai, Liu, Qingxin, Cui, Meng, Zhou, Zizhang
Format: Article
Language:English
Subjects:
Adaptor Proteins, Signal Transducing - metabolism
Animals
ARRDC3
Arrestins - metabolism
Carcinogenesis
Cell Line, Tumor
Cell Proliferation
colorectal cancer
Colorectal Neoplasms - metabolism
Colorectal Neoplasms - pathology
Disease Progression
Down-Regulation
Hippo pathway
Humans
Neoplasm Metastasis
Phosphoproteins - metabolism
Protein Stability
Proteolysis
Transcription Factors
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Summary: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 (ARRDC3) has been reported to promote lysosome‐mediated protein degradation. In the present study, we find that the expression of ARRDC3 is downregulated in CRC specimens. Mechanistically, we reveal that ARRDC3 binds and decreases expression of the oncoprotein YAP, the cotranscription factor of the Hippo pathway. The regulation of the Hippo pathway by ARRDC3 is conserved from Drosophila to mammals. Furthermore, we demonstrate that ARRDC3 plays an anti‐oncogenic role in CRC progression by promoting YAP degradation. Finally, we show that ARRDC3 increases the sensitivity of CRC cells toward chemotherapeutic drugs. Taken together, our findings point to ARRDC3 as a potential target for CRC treatment.
ISSN:0014-5793
1873-3468
DOI:10.1002/1873-3468.12986