ROCK2 disturbs MKP1 expression to promote invasion and metastasis in hepatocellular carcinoma.
ROCK2 disturbs MKP1 expression to promote invasion and metastasis in hepatocellular carcinoma.
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ROCK2 干扰 MKP1 表达促进肝细胞癌的侵袭和转移。
DOI：
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发表时间：
2020-03
影响因子：
5.3
通讯作者：
Zhou W
中科院分区：
文献类型：
--
作者：
Du Y;Lu S;Ge J;Long D;Wen C;Tan S;Chen L;Zhou W
双特异性磷酸酶-1（DUSP1/MKP1）在控制肿瘤转移和侵袭等多种生理和病理现象中发挥着关键作用。然而，MKP1在肿瘤发生中的作用存在争议。我们发现，肝细胞癌（HCC）中 MKP1 的表达显着下调，并且 MKP1 是不良预后的独立预测因子。在体外和体内研究中，我们发现MKP1显着抑制HCC细胞的侵袭和转移。此外，我们发现 MKP1 低表达与 ROCK2 表达相关，ROCK2 在 HCC 中发挥重要作用。我们的数据表明 MKP1 对于 ROCK2 介导的转移和侵袭至关重要。有趣的是，我们证明ROCK2对MKP1的蛋白质和mRNA水平具有相反的影响，因为它降低蛋白质水平的表达并增加mRNA水平的表达。我们还确定了造成这种不一致的机制； ROCK2 激活 ERK1/2-ATF2 信号传导，导致 MKP1 mRNA 表达增加。同时，ROCK2通过激活ERK1/2促进泛素介导的MKP1降解，从而促进HCC的转移。总之，我们的数据为 MKP1 作为潜在生物标志物的生物学和临床意义提供了新的证据。我们证明 ROCK2 会干扰人类 HCC 进展中 MKP1 的蛋白质和 mRNA 表达。
Dual-specificity phosphatase-1 (DUSP1/MKP1) plays a key role in controlling various physiological and pathological phenomena, including tumor metastasis and invasion. However, the role of MKP1 in tumorigenesis is controversial. We showed that the expression of MKP1 in hepatocellular carcinoma (HCC) is significantly downregulated, and MKP1 is an independent predictor of poor prognosis. In in vitro and in vivo studies, we showed that MKP1 significantly inhibits the invasion and metastasis of HCC cells. Additionally, we found that low MKP1 expression is associated with the expression of ROCK2, which plays an important role in HCC. Our data suggest that MKP1 is crucial for ROCK2-mediated metastasis and invasion. Interestingly, we demonstrated that ROCK2 has opposite effects on protein and mRNA levels of MKP1, as it decreases the expression at the protein level and increases the expression at the mRNA level. We also identified the mechanism responsible for this incongruency; ROCK2 activates ERK1/2-ATF2 signaling, which leads to the increased mRNA expression of MKP1. At the same time, ROCK2 promotes the ubiquitin-mediated degradation of MKP1 by activating ERK1/2, therefore promoting the metastasis of HCC. In conclusion, our data provide new evidence for the biological and clinical significance of MKP1 as a potential biomarker. We demonstrate that ROCK2 disturbs the protein and mRNA expression of MKP1 in human HCC progression.
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DOI：
10.1016/j.jss.2009.01.031
发表时间：
2010-11
期刊：
The Journal of surgical research
影响因子：
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作者：
Huan N Vu;Walter Miller;Sarah O'Connor;Mei He;P. Schafer;F. Payvandi;G. Muller;D. Stirling;S. Libutti
通讯作者：
Huan N Vu;Walter Miller;Sarah O'Connor;Mei He;P. Schafer;F. Payvandi;G. Muller;D. Stirling;S. Libutti
影响因子：
--
作者：
Shen J;Zhou S;Shi L;Liu X;Lin H;Yu H;Xiaoliang;Tang J;Yu T;Cai X
通讯作者：
Cai X
影响因子：
13.5
作者：
Wong, Carmen Chak-Lui;Wong, Chun-Ming;Ng, Irene Oi-Lin
通讯作者：
Ng, Irene Oi-Lin
Rho激酶（岩石）信号传导的抑制剂在3D背景下恢复了乳腺癌细胞的恶性表型。
影响因子：
--
作者：
Matsubara M;Bissell MJ
通讯作者：
Bissell MJ
影响因子：
11.2
作者：
Candas D;Lu CL;Fan M;Chuang FY;Sweeney C;Borowsky AD;Li JJ
通讯作者：
Li JJ