文章：

GINS2通过特异性刺激ERK/MAPK信号传导促进胰腺癌的EMT

GINS2 promotes EMT in pancreatic cancer via specifically stimulating ERK/MAPK signaling 

原文发布日期：2020-08-03 

英文摘要：

Go-Ichi-Ni-San 2 (GINS2), as a newly discovered oncogene, is overexpressed in several cancers. However, the specific role of GINS2 in the development of pancreatic cancer (PC), to our knowledge, is poorly understood. We systematically explored the potential role of GINS2 in epithelial–mesenchymal-transition (EMT)-stimulated PC in vitro and vivo. GINS2 was overexpressed in human PC specimens, which was positively associated with tumor size (P = 0.010), T stage (P = 0.006), vascular invasion (P = 0.037), and the poor prognosis (P = 0.004). Interestingly, a close correlation between GINS2, E-cadherin, and Vimentin (P = 0.014) was found in human PC specimens and cell lines that coordinately promoted the worse survival of PC patients (P = 0.009). GINS2 overexpression stimulated EMT in vitro, including promoting EMT-like cellular morphology, enhancing cell motility, and activating EMT and ERK/MAPK signal pathways. However, PD98059, a specific MEK1 inhibitor, reversed GINS2 overexpression-stimulated EMT in vitro. Conversely, GINS2 silencing inhibited EMT in PANC-1 cells, which was also rescued by GINS2-GFP. Moreover, GINS2 was colocalized and co-immunoprecipitated with ERK in GINS2 high-expression Miapaca-2 and PANC-1 cells, implying a tight interaction of GINS2 with ERK/MAPK signaling. Meanwhile, GINS2 overexpression inhibited distant liver metastases in vivo, following a tight association with EMT and ERK/MAPK signaling, which was reversed by MEK inhibitor. Overexpression of GINS2 contributes to advanced clinical stage of PC patient and promotes EMT in vitro and vivo via specifically activating ERK/MAPK signal pathway. 

摘要翻译： 

Go-Ichi-Ni-San 2（GINS2）作为一种新发现的癌基因，在多种癌症中过度表达。然而据我们所知，GINS2在胰腺癌（PC）发展中的具体作用尚不明确。我们通过体外和体内实验系统探讨了GINS2在上皮-间质转化（EMT）激发的胰腺癌中的潜在作用。GINS2在人类胰腺癌标本中过度表达，且与肿瘤大小（P=0.010）、T分期（P=0.006）、血管侵犯（P=0.037）及不良预后（P=0.004）呈正相关。值得注意的是，在人类胰腺癌标本和细胞系中，GINS2与E-钙黏蛋白、波形蛋白（Vimentin）存在密切关联（P=0.014），三者协同作用导致胰腺癌患者生存期缩短（P=0.009）。体外实验中GINS2过表达通过激活EMT和ERK/MAPK信号通路，诱导EMT样细胞形态转变并增强细胞运动能力。而特异性MEK1抑制剂PD98059可逆转GINS2过表达刺激的EMT现象。相反，沉默GINS2可抑制PANC-1细胞的EMT过程，该效应可被GINS2-GFP恢复。在GINS2高表达的Miapaca-2和PANC-1细胞中，GINS2与ERK共定位并发生免疫共沉淀，提示GINS2与ERK/MAPK信号通路存在紧密相互作用。同时，体内实验表明GINS2过表达通过EMT和ERK/MAPK信号通路抑制远处肝转移，该过程可被MEK抑制剂逆转。GINS2过表达不仅与胰腺癌患者临床分期进展相关，更通过特异性激活ERK/MAPK信号通路在体外和体内促进EMT进程。

原文链接：

GINS2 promotes EMT in pancreatic cancer via specifically stimulating ERK/MAPK signaling