College of Life Sciences, Shandong Agricultural University, Tai'an, Shandong, China.
Department of Anorectum, Qianfo Mount Hospital affiliated to Shandong University, Ji'nan, Shandong, China.
FEBS Lett. 2018 Feb;592(4):599-609. doi: 10.1002/1873-3468.12986. Epub 2018 Feb 13.
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.
虽然结直肠癌（CRC）是一种常见的消化系统恶性肿瘤，但 CRC 肿瘤发生的潜在机制仍难以捉摸。有报道称， arrestin 相关结构域蛋白 3（ARRDC3）可促进溶酶体介导的蛋白质降解。在本研究中，我们发现 ARRDC3 在 CRC 标本中的表达下调。从机制上讲，我们揭示了 ARRDC3 结合并降低了 Hippo 通路转录共激活因子 YAP 的表达。从果蝇到哺乳动物，ARRDC3 对 Hippo 通路的调控是保守的。此外，我们证明 ARRDC3 通过促进 YAP 降解在 CRC 进展中发挥抑癌作用。最后，我们发现 ARRDC3 增加了 CRC 细胞对化疗药物的敏感性。总之，我们的研究结果表明 ARRDC3 可能成为 CRC 治疗的潜在靶点。
