Monopolar spindle-one-binder protein 2 regulates the activity of large tumor suppressor/yes-associated protein to inhibit the motility of SMMC-7721 hepatocellular carcinoma cells

被引:7
|
作者
Zhang, Weicheng [1 ]
Shen, Jingyuan [1 ]
Gu, Fengming [1 ]
Zhang, Ying [1 ]
Wu, Wenjuan [1 ,2 ]
Weng, Jiachun [1 ]
Liao, Yuexia [1 ]
Deng, Zijing [1 ]
Yuan, Qing [1 ]
Zheng, Lu [1 ]
Zhang, Yu [1 ,3 ,4 ]
Shen, Weigan [1 ,3 ,4 ]
机构
[1] Yangzhou Univ, Sch Med, Dept Cell Biol, 11 Huaihai Rd, Yangzhou 225001, Jiangsu, Peoples R China
[2] Yangzhou Univ, Dept Med Oncol, Clin Med Coll, Yangzhou 225001, Jiangsu, Peoples R China
[3] Jiangsu Coinnovat Ctr Prevent & Control Important, Yangzhou 225009, Jiangsu, Peoples R China
[4] Jiangsu Key Lab Integrated Tradit Chinese & Weste, Yangzhou 225001, Jiangsu, Peoples R China
关键词
monopolar spindle-one-binder protein 2; hippo pathway; yes-associated protein; nuclear-Dbf2-related kinase; large tumor suppressor; HIPPO-PATHWAY; KINASE; YAP; PHOSPHORYLATION; PROLIFERATION; EXPRESSION; MECHANISM; INVASION; FAMILY; LATS1;
D O I
10.3892/ol.2018.7952
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Accumulating evidence implicates mono polar spindle-one-hinder protein (MOB)2 as an inhibitor of nrielear-Dbf2-related kinase (NDR) by competing with MOBI for interaction with NDRE2. NDR/large tumor suppressor (LATS) kinases may function similarly to yes-associated protein (YAP) kinases and be considered as members of the Hippo core cassette. 1\40132 appears to serve roles in cell survival, cell cycle progression, responses to DNA damage and cell motility. However, the underlying mechanisms involved remain unclaritied. In the present study, it was demonstrated that the knockout of MOB2 by clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR associated protein 9 promoted migration and invasion, induced phosphorylation of NDRE2 and decreased phosphorylation of YAP in SMMC-7721 cells when compared with the blank vector-transduced cells. By contrast, the overexpression of MOB2 resulted in the opposite results. Mechanistically, MOB2 regulated the alternative interaction of MOR1 with NDRE2 and LATS 1, which resulted in increased phosphorylation of LAM and MOB and thereby led to the inactivation of YAP and consequently inhibition of cell motility. The results of the present study provide evidence of MOB2 serving a positive role in LATS/YAP activation by activating the Hippo signaling pathway.
引用
收藏
页码:5375 / 5383
页数:9
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