Department of Ultrasound, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200080, China.
Department of Instrument Science and Engineering, Shanghai Jiao Tong University, Shanghai, 200240, China.
Hum Cell. 2020 Oct;33(4):1186-1196. doi: 10.1007/s13577-020-00401-2. Epub 2020 Jul 22.
Pancreatic cancer is the fourth most common lethal malignancy with an overall 5-year survival rate of less than 5%. ERas, a novel Ras family member, was first identified in murine embryonic stem cells and is upregulated in various cancers. However, the expression and potential role of ERas in pancreatic cancer have not been investigated. In this study, we found that ERas mRNA and protein were upregulated in pancreatic cancer tissues and cells compared with controls. Knockdown of ERas in pancreatic cancer cells by siRNA significantly decreased cell proliferation, colony formation, migration, and invasion and promoted cell apoptosis in vitro. Epithelial-mesenchymal transition (EMT) is closely related to tumor progression. We observed a significant decrease in N-cadherin expression in pancreatic cancer cells in response to ERas gene silencing by immunofluorescence assay and western blot. Furthermore, tumor growth and EMT were inhibited in xenografts derived from pancreatic cancer cells with ERas downregulation. We further investigated the regulatory mechanisms of ERas in pancreatic cancer and found that ERas may activate the Erk/Akt signaling pathway. Moreover, Erk inhibitor decreased pancreatic cancer cells proliferation and colony formation activities. Our data suggest that targeting ERas and its relevant signaling pathways might represent a novel therapeutic approach for the treatment of pancreatic cancer.
胰腺癌是第四种常见的致命恶性肿瘤，整体 5 年生存率低于 5%。ERas 是 Ras 家族的一个新成员，最初在鼠胚胎干细胞中被发现，在各种癌症中上调。然而，ERas 在胰腺癌中的表达和潜在作用尚未被研究。在这项研究中，我们发现 ERas mRNA 和蛋白在胰腺癌组织和细胞中上调，与对照组相比。用 siRNA 敲低胰腺癌细胞中的 ERas 显著减少了细胞增殖、集落形成、迁移和侵袭，并促进了细胞凋亡。上皮-间充质转化（EMT）与肿瘤进展密切相关。我们通过免疫荧光和 Western blot 观察到，ERas 基因沉默后，胰腺癌细胞中 N-钙粘蛋白的表达明显下降。此外，在下调 ERas 的胰腺癌细胞来源的异种移植瘤中，肿瘤生长和 EMT 受到抑制。我们进一步研究了 ERas 在胰腺癌中的调控机制，发现 ERas 可能激活了 Erk/Akt 信号通路。此外，Erk 抑制剂降低了胰腺癌细胞的增殖和集落形成活性。我们的数据表明，靶向 ERas 及其相关信号通路可能代表治疗胰腺癌的一种新的治疗方法。
