GRK2 Suppresses Hepatocellular Carcinoma Metastasis and Invasion Through Down-Regulation of Prostaglandin E Receptor 2.
GRK2 Suppresses Hepatocellular Carcinoma Metastasis and Invasion Through Down-Regulation of Prostaglandin E Receptor 2.
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GRK2 通过下调前列腺素 E 受体 2 抑制肝细胞癌转移和侵袭。
DOI：
10.2147/ott.s266641
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发表时间：
2020
影响因子：
4
通讯作者：
Sun WY
中科院分区：
文献类型：
--
作者：
Li N;Wu JJ;Chen TT;Li XQ;Du JJ;Shan S;Wei W;Sun WY
肝细胞癌（HCC）是一种侵袭性的人类肝癌，是全球第五大常见恶性肿瘤。由于常规治疗效果不佳，临床急需新的有效治疗策略。G蛋白偶联受体激酶（GRKs），包括GRK2和GRK3，已知参与各种必需的细胞过程并调节许多信号通路。然而，GRK2/3在HCC侵袭和转移中的作用仍不清楚。采用免疫组化、Western blot、激光共聚焦显微镜和qRT-PCR检测肝癌患者和DEN诱导的肝癌小鼠肝组织中GRK2/3和EP2的表达。采用创伤愈合法和transwell法检测转染GRK2 siRNA后肝癌细胞的迁移和侵袭能力。Western blot检测Akt和ERK的下游通路。肝癌组织中GRK2的表达明显低于癌旁组织，GRK3的表达无明显变化。此外，GRK2的表达减少，在肝肿瘤的发生过程中，二乙基亚硝胺诱导的肝癌模型。此外，我们的体外研究表明，随着肝癌细胞系转移潜能的增加，GRK2表达逐渐降低，GRK2敲低显著促进肝癌细胞的迁移和侵袭。GRK2低表达与EP2受体转位至细胞膜表达增加及Akt通路激活有关。提示GRK2可能通过调节EP2受体转位抑制HCC的转移和侵袭，且这种作用可能是通过Akt途径介导的。
Hepatocellular carcinoma (HCC) is an aggressive form of human liver cancer and the fifth most common malignancy worldwide. Novel effective treatment strategies for HCC are urgently in clinical because of its poor response to conventional therapies. G protein-coupled receptor kinases (GRKs), including GRK2 and GRK3, are known that involves in various essential cellular processes and regulates numerous signaling pathways. However, the role of GRK2/3 in invasion and metastasis of HCC still remains unclear. Immunohistochemistry, Western blot, laser confocal microscopy and qRT-PCR were used to detect the expression of GRK2/3 and EP2 in liver tissues of HCC patients and DEN-induced HCC mice. Wound healing and transwell assay were applied to measure the migration and invasion of HCC cells after transfected with GRK2 siRNA. The downstream pathway of Akt and ERK was verified by Western blot. The expression of GRK2 was significantly decreased, while GRK3 was not significantly changed in HCC tissues compared with noncancerous tissues of HCC patients. Moreover, GRK2 expression was reduced during liver tumorigenesis in diethylnitrosamine-induced liver tumor model. In addition, our in vitro study showed that GRK2 expression was gradually decreased with increasing HCC cell line metastatic potential, and GRK2 knockdown significantly promoted the migration and invasion of HCC cells. Furthermore, low GRK2 expression was associated with increased expression of EP2 receptor translocation to HCC cell membrane, and the activation of Akt pathway. These data suggest that GRK2 inhibits HCC metastasis and invasion may be through regulating EP2 receptor translocation, and this effect appears to be mediated by Akt pathway.
DOI：
10.5114/wo.2015.51417
发表时间：
2015
期刊：
Contemporary oncology (Poznan, Poland)
影响因子：
--
作者：
Mochocki M;Morawski P;Kopta R;Brzezińska-Błaszczyk E;Stasikowska O;Lewy-Trenda I;Student Scientific Circle;Starska K
通讯作者：
Starska K