Ephexin1 cooperates with K-Ras to promote oncogenic Ras-driven tumorigenesis

Ephexin1 was initially identified as a neuronal guanine nucleotide exchange factor involved in the control of neuronal development and synaptic homeostasis. Here, we demonstrate that the induction of Ephexin1 expression by an oncogenic K-Ras mutation amplifies the MAPK signaling via direct interaction with oncogenic Ras and contributes to colon and lung tumorigenesis. Ephexin1 cooperates with mutant Ras to accelerate skin tumorigenesis in vivo. In addition, we have demonstrated that the functionally relevant interaction between oncogenic K-Ras and Ephexin1. Together, these findings suggest that Ephexin1 serves as a positive regulator of Ras-driven oncogenesis and potentially represents a novel target for therapeutic intervention. Overall design: To determine whether change of mRNA by Ephexin1, we examined in shControl_H1299 cells and shEphexin1_H1299 cells were compared.

Ephexin1 最初被鉴定为一种参与神经元发育与突触稳态调控的神经元型鸟苷酸交换因子（neuronal guanine nucleotide exchange factor）。本研究证实，致癌性K-Ras突变诱导的Ephexin1表达可通过与致癌性Ras的直接相互作用增强丝裂原活化蛋白激酶（mitogen-activated protein kinase, MAPK）信号通路，进而促进结直肠癌与肺癌的肿瘤发生。Ephexin1可与突变型Ras协同，在体内加速皮肤肿瘤的发生发展。此外，本研究证实了致癌性K-Ras与Ephexin1之间存在功能相关性相互作用。综上，上述研究结果表明，Ephexin1可作为Ras驱动的肿瘤发生的正向调控因子，有望成为肿瘤治疗的新型干预靶点。整体实验设计：为明确Ephexin1对mRNA表达的调控作用，本研究以shControl_H1299细胞与shEphexin1_H1299细胞为模型开展对比分析。