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.

Go-Ichi-Ni-San 2 (GINS2) 作为一种新发现的致癌基因，在几种癌症中过度表达。然而，据我们所知，人们对 GINS2 在胰腺癌 (PC) 发展中的具体作用知之甚少。我们在体外和体内系统地探索了 GINS2 在上皮间质转化 (EMT) 刺激的 PC 中的潜在作用。GINS2在人PC标本中过表达，与肿瘤大小（P  =0.010）、T分期（P  =0.006）、血管侵犯（P  =0.037）和预后不良（P  =0.004）呈正相关。有趣的是，GINS2、E-cadherin 和 Vimentin 之间密切相关（P = 0.014) 在人类 PC 标本和细胞系中发现协同促进 PC 患者更差的生存 ( P = 0.009)。GINS2 过表达在体外刺激 EMT，包括促进 EMT 样细胞形态、增强细胞运动以及激活 EMT 和 ERK/MAPK 信号通路。然而，一种特定的 MEK1 抑制剂 PD98059 在体外逆转了 GINS2 过表达刺激的 EMT。相反，GINS2 沉默抑制 PANC-1 细胞中的 EMT，这也被 GINS2-GFP 拯救。此外，在 GINS2 高表达 Miapaca-2 和 PANC-1 细胞中，GINS2 与 ERK 共定位并共免疫沉淀，这意味着 GINS2 与 ERK/MAPK 信号传导密切相互作用。同时，GINS2 过表达可抑制体内远处肝转移，这与 EMT 和 ERK/MAPK 信号传导密切相关，而 MEK 抑制剂可逆转该信号。