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ARRDC3 suppresses colorectal cancer progression through destabilizing the oncoprotein YAP
Author(s) -
Shen Xu,
Sun Xiaohan,
Sun Bing,
Li Tao,
Wu Guoliang,
Li Yuantao,
Chen Lai,
Liu Qingxin,
Cui Meng,
Zhou Zizhang
Publication year - 2018
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.12986
Subject(s) - colorectal cancer , hippo signaling pathway , cancer research , carcinogenesis , biology , cancer , mouse model of colorectal and intestinal cancer , malignancy , microbiology and biotechnology , signal transduction , genetics
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.