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The MAP kinase-interacting kinases (MNKs) as targets in oncology

机译：地图激酶 - 相互作用的激酶（MNK）作为肿瘤学的靶标

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Introduction: The mitogen-activated protein kinase (MAPK)-interacting kinases (MNKs) are switched on by the oncogenic MAPK (ERK) signalling pathway. They phosphorylate eukaryotic initiation factor (eIF) 4E, a protein which recruits ribosomes to mRNAs and thereby mediates their translation. Importantly, overexpression of eIF4E can transform cells, and its function is controlled by a second oncogenic pathway, mechanistic target of rapamycin complex 1. Areas covered: We have evaluated the literature related to the role of the MNKs in human cancers, including their control by oncogenic signalling pathways; their expression and regulation in cancer cells and preclinical cancer models; and their roles in the proliferation, survival and migration/invasion of cancer cells. We also discuss progress towards generating specific and potent inhibitors of the MNKs and data obtained using such compounds. Expert opinion: The available data indicate that MNKs and/or eIF4E phosphorylation play a role in oncogenic transformation, the progression of at least some tumours and especially in processes related to tumour metastasis. MNKs are clearly druggable targets and, as they are not essential, significant 'side effects' of inhibiting the MNKs are likely to be limited. Further work is required to assess the efficacy of MNK inhibition in tackling tumour development, progression and metastasis.
机译：引言：通过致癌MAPK（ERK）信号通路接通丝肠激活蛋白激酶（MAPK） - 交互激酶（MNK）。它们磷酸化真核引发因子（EIF）4e，一种促进MRNA的核糖体的蛋白质，从而介导它们的翻译。重要的是，EIF4E的过表达可以转化细胞，其功能由第二个致癌途径控制，雷帕霉素复合物的机械靶标。所涵盖的区域：我们已经评估了与人类癌症中MNK的作用有关的文献，包括他们的控制致癌信号通路;它们在癌细胞和临床前癌症模型中的表达和调节;及其在癌细胞增殖，存活和迁移/侵袭中的作用。我们还讨论了产生了使用这些化合物获得的MNK和数据的特定和有效抑制剂的进展。专家意见：可用数据表明MNK和/或EIF4E磷酸化在致癌转化中发挥作用，至少一些肿瘤的进展，特别是在与肿瘤转移相关的过程中。 MNKs是明显的可用性目标，因为它们不是必需的，抑制MNK的重要性“副作用”可能有限。需要进一步的工作来评估MNK抑制在应对肿瘤发育，进展和转移方面的疗效。

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