TRIP suppresses cell proliferation and invasion in choroidal melanoma via promoting the proteasomal degradation of Twist1

被引:10
|
作者
Wei, Chao [1 ]
Zhao, Xiaofei [1 ]
Wang, Lei [1 ]
Zhang, Han [1 ]
机构
[1] Shandong Univ, Cheeloo Coll Med, Hosp 2, Dept Ophthalmol, Jinan 250033, Shandong, Peoples R China
基金
中国国家自然科学基金;
关键词
choroidal melanoma; EMT; TRIP; Twist1; INTERACTING PROTEIN TRIP; TO-MESENCHYMAL TRANSITION; PHOSPHORYLATION; METASTASIS; KINASE; BINDING; SNAIL; EMT;
D O I
10.1002/1873-3468.13882
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Choroidal melanoma (CM) remains the most prevalent form of intraocular malignancy, and the prognosis of affected patients is poor. While the E3 ubiquitin ligase TRAF-interacting protein (TRIP) is known to play key regulatory roles in multiple diseases, its relevance in CM remains uncertain. In the present study, we found that TRIP overexpression is sufficient to inhibit the proliferation, invasion, and epithelial-mesenchymal transition (EMT) of CM cellsin vitro, whereas the opposite phenotypes are observed following TRIP knockdown. We further determined that TRIP is able to promote the K48-polyubiquitination of EMT-associated transcription factor Twist-related protein 1, thereby suppressing EMT progression. Together, our results suggest that TRIP plays an important role in regulating the progression of CM and that it may therefore be an important therapeutic target for the treatment of this disease.
引用
收藏
页码:3170 / 3181
页数:12
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