R-spondin3 promotes the tumor growth of choriocarcinoma JEG-3 cells
R-spondin3 promotes the tumor growth of choriocarcinoma JEG-3 cells
复制标题
R-Spondin3 促进绒毛膜癌 JEG-3 细胞的肿瘤生长。
DOI：
10.1152/ajpcell.00295.2019
复制
发表时间：
2020-03-01
影响因子：
5.5
通讯作者：
Yang, Qing
中科院分区：
文献类型：
--
作者：
Chen, Zhilong;Zhang, Juzuo;Yang, Qing
R-spondin 3（RSPO 3）是Wnt/β-catenin信号通路的激活剂，在多种肿瘤的发生中起关键作用，但其在绒毛膜癌中的作用尚不清楚。为探讨RSPO 3对绒毛膜癌JEG-3细胞生长的影响，检测RSPO 3在人足月胎盘组织中的表达，并通过慢病毒介导的转染建立稳定过表达RSPO 3的JEG-3细胞系。在RSPO 3过表达的JEG-3细胞中检测与致瘤性相关的生物标志物的表达，并研究细胞增殖、侵袭、迁移和凋亡。此外，进行软琼脂克隆形成试验和异种移植物致瘤性试验，以评估RSPO 3对体外和体内肿瘤生长的影响。结果表明，RSPO 3在人足月胎盘中广泛表达，过表达RSPO 3可促进JEG-3细胞的增殖，抑制其迁移、侵袭和凋亡。同时，RSPO 3过表达促进肿瘤生长在体内和体外。进一步的研究表明，RSPO 3过表达的JEG-3细胞和肿瘤移植物中Akt、PI 3 K和ERK的磷酸化水平以及β-catenin和增殖细胞核抗原（PCNA）的表达均增加。综上所述，这些数据表明RSPO 3通过Akt/PI 3 K/ERK信号传导促进绒毛膜癌的肿瘤生长，这支持RSPO 3作为促进绒毛膜癌进展的致癌驱动因子。
R-spondin3 (RSPO3), an activator of Wnt/β-catenin signaling, plays a key role in tumorigenesis of various cancers, but its role in choriocarcinoma remains unknown. To investigate the effect of RSPO3 on the tumor growth of choriocarcinoma JEG-3 cells, the expression of RSPO3 in human term placenta was detected, and a stable RSPO3-overexpressing JEG-3 cell line was established via lentivirus-mediated transduction. The expression of biomarkers involved in tumorigenicity was detected in the RSPO3-overexpressing JEG-3 cells, and cell proliferation, invasion, migration, and apoptosis were investigated. Moreover, soft agar clonogenic assays and xenograft tumorigenicity assays were performed to assess the effect of RSPO3 on tumor growth in vitro and in vivo. The results showed that RSPO3 was widely expressed in human term placenta and overexpression of RSPO3 promoted the proliferation and inhibited the migration, invasion, and apoptosis of the JEG-3 cells. Meanwhile, RSPO3 overexpression promoted tumor growth both in vivo and in vitro. Further investigation showed that the phosphorylation levels of Akt, phosphatidylinositol 3-kinase (PI3K), and ERK as well the expression of β-catenin and proliferating cell nuclear antigen (PCNA) were increased in the RSPO3-overexpressing JEG-3 cells and tumor xenograft. Taken together, these data indicate that RSPO3 promotes the tumor growth of choriocarcinoma via Akt/PI3K/ERK signaling, which supports RSPO3 as an oncogenic driver promoting the progression of choriocarcinoma.