Department of Biochemistry and Molecular Biology, Capital Medical University, Beijing 100069, P.R. China.
Int J Oncol. 2016 Oct;49(4):1737-45. doi: 10.3892/ijo.2016.3655. Epub 2016 Aug 11.
Ezrin-radixin-moesin-binding phosphoprotein-50 (EBP50) has a role in the occurrence and progression of multiple types of tumors. However, its role in cervical cancer (CC) remain unknown. EBP50 was reported to interact with epidermal growth factor receptor (EGFR) and regulate EGFR signaling in CC HeLa cells. In this study, the effect of EBP50 expression on CC cell proliferation and prognosis of CC patients by regulating EGFR signaling was investigated. We found that EBP50 expression level was significantly downregulated in CC tissues. EBP50 expression negatively correlated with CC cell proliferation, cell cycle and the activation of EGFR-mediated ERK signaling. EBP50 knockdown abolished its inhibition on EGF-induced ERK activation, suggesting EBP50 regulated EGFR signaling. In order to further explore EBP50 regulated EGFR signaling via interaction, we constructed EBP50_DD mutant which disrupted its interaction with EGFR. EBP50_DD overexpression attenuated the inhibition of EBP50_WT on EGFR-mediated ERK signaling, further revealing EBP50 regulated EGFR signaling via its interaction with EGFR. EGFR activation was associated with poor prognosis of CC patients. EBP50 could not predict the prognosis of all CC patients. However, after ruling out patients with egfr/ErbB mutation or copy number variation (CNV) and (chemo)radiation, which caused continuous EGFR activation and affected the prognosis of patients, respectively, EBP50 expression level exhibited the prognosis prediction ability, revealing EBP50 affected prognosis of CC patients via regulating EGFR signaling. In conclusion, EBP50 played an important role in CC cell proliferation and prognosis prediction of CC patients by interacting with EGFR and regulating EGFR signaling. EBP50 might be a potential precise therapeutic target or prognostic marker for CC patients.
埃兹蛋白-根蛋白-膜突蛋白结合磷蛋白 50（EBP50）在多种类型肿瘤的发生和发展中起作用。然而，其在宫颈癌（CC）中的作用尚不清楚。有报道称，EBP50 与表皮生长因子受体（EGFR）相互作用，并调节 CC HeLa 细胞中的 EGFR 信号。在本研究中，通过调节 EGFR 信号研究了 EBP50 表达对 CC 细胞增殖和 CC 患者预后的影响。我们发现 EBP50 在 CC 组织中的表达水平显著下调。EBP50 的表达与 CC 细胞增殖、细胞周期和 EGFR 介导的 ERK 信号激活呈负相关。EBP50 敲低消除了其对 EGF 诱导的 ERK 激活的抑制作用，表明 EBP50 调节 EGFR 信号。为了进一步探讨 EBP50 通过相互作用调节 EGFR 信号，我们构建了破坏其与 EGFR 相互作用的 EBP50_DD 突变体。EBP50_DD 过表达减弱了 EBP50_WT 对 EGFR 介导的 ERK 信号的抑制作用，进一步揭示 EBP50 通过与 EGFR 的相互作用调节 EGFR 信号。EGFR 激活与 CC 患者的不良预后相关。EBP50 不能预测所有 CC 患者的预后。然而，在排除了引起 EGFR 持续激活并影响患者预后的 egfr/ErbB 突变或拷贝数变异（CNV）以及（化疗）放疗的患者后，EBP50 的表达水平显示出了预后预测能力，表明 EBP50 通过调节 EGFR 信号影响 CC 患者的预后。总之，EBP50 通过与 EGFR 相互作用并调节 EGFR 信号，在 CC 细胞增殖和 CC 患者预后预测中发挥重要作用。EBP50 可能是 CC 患者潜在的精确治疗靶点或预后标志物。
