Department of Thoracic Surgery, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
Guangzhou Research Institute of Respiratory Disease, Guangzhou, China.
Sci Rep. 2017 Sep 6;7(1):10612. doi: 10.1038/s41598-017-10397-9.
We hypothesized that MAP kinase-interacting serine/threonine kinase 2 (MNK2) may contribute to non-small cell lung cancer (NSCLC) development, and serve as a new therapeutic target. Immunohistochemical staining evaluated the correlation between MNK2 expression and clinicopathological features in 367 NSCLC cancer tissues. We determined the effects of MNK2 silencing in NSCLC cell lines in vitro and in vivo. RT-PCR and western blotting was used to examine the impact of MNK2 on ERK and AKT pathways. MNK2 was overexpressed in NSCLC cell lines and tumor tissues. Patients with MNK2 overexpression had lower OS rates (P < 0.001). High expression of MNK2 was correlated with lymph node metastasis (P = 0.008). MNK2 functioned as an independent prognostic factor for poor survival in patients with NSCLC (P = 0.003). MNK2 down-regulation inhibited proliferation, migration and invasion in vitro (P < 0.001), and reduced tumor growth and invasion in nude mice (P < 0.05). MNK2 enhanced phosphorylation of eIF4E, a downstream target of ERK and AKT pathways, which promoted NSCLC proliferation and invasion. We conclude that MNK2 overexpression in NSCLC is associated with proliferation, migration, invasion, and lower survival rates in patients via the phosphorylated eIF4E-mediated signaling pathway.
我们假设丝氨酸/苏氨酸激酶 2（MNK2）可能有助于非小细胞肺癌（NSCLC）的发展，并可作为新的治疗靶点。免疫组织化学染色评估了 367 例 NSCLC 癌组织中 MNK2 表达与临床病理特征的相关性。我们在体外和体内确定了 MNK2 沉默对 NSCLC 细胞系的影响。RT-PCR 和 Western blot 用于检查 MNK2 对 ERK 和 AKT 通路的影响。MNK2 在 NSCLC 细胞系和肿瘤组织中过表达。MNK2 过表达的患者 OS 率较低（P<0.001）。MNK2 的高表达与淋巴结转移相关（P=0.008）。MNK2 是 NSCLC 患者不良生存的独立预后因素（P=0.003）。MNK2 下调抑制了体外增殖、迁移和侵袭（P<0.001），并减少了裸鼠肿瘤生长和侵袭（P<0.05）。MNK2 增强了 eIF4E 的磷酸化，ERK 和 AKT 通路的下游靶点，促进了 NSCLC 的增殖和侵袭。我们得出结论，MNK2 在 NSCLC 中的过表达与增殖、迁移、侵袭以及患者生存率降低有关，其通过磷酸化 eIF4E 介导的信号通路发挥作用。
