Synergistic effects of inhibiting the MNK-eIF4E and PI3K/AKT/ mTOR pathways on cell migration in MDA-MB-231 cells.
Synergistic effects of inhibiting the MNK-eIF4E and PI3K/AKT/ mTOR pathways on cell migration in MDA-MB-231 cells.
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DOI：
10.18632/oncotarget.24354
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发表时间：
2018-03-06
期刊：
影响因子：
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通讯作者：
Morley SJ
中科院分区：
文献类型：
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作者：
Lineham E;Tizzard GJ;Coles SJ;Spencer J;Morley SJ
真核起始因子 4E (eIF4E) 的研究是癌症研究的一个重点，因为它在控制肿瘤相关蛋白的翻译中发挥作用，从而驱动侵袭性迁移表型。 eIF4E 是 eIF4F 复合物的限制性成分，而 eIF4F 复合物是 mRNA 翻译的关键决定因素。丝裂原激活蛋白激酶相互作用蛋白激酶 (MNK1/2) 磷酸化 Ser209 上的 eIF4E，促进致癌蛋白的表达，而 mTORC1 磷酸化并失活 eIF4E 抑制剂 4E-BP1，以释放翻译抑制。在这里，我们证明同时抑制这些途径可以有效减慢乳腺癌细胞的细胞迁移速度。然而，使用新型可裂解双重 MNK1/2 和 PI3K/mTOR 抑制杂合剂的分子杂交方法在减缓细胞迁移方面效果较差。
The study of eukaryotic initiation factor 4E (eIF4E) is a key focus in cancer research due to its role in controlling the translation of tumour-associated proteins, that drive an aggressive migratory phenotype. eIF4E is a limiting component of the eIF4F complex which is a critical determinant for the translation of mRNAs. Mitogen-activated protein kinase interacting protein kinases (MNK1/2) phosphorylate eIF4E on Ser209, promoting the expression of oncogenic proteins, whereas mTORC1 phosphorylates and de-activates the eIF4E inhibitor, 4E-BP1, to release translational repression. Here we show that inhibiting these pathways simultaneously effectively slows the rate of cell migration in breast cancer cells. However, a molecular hybridisation approach using novel, cleavable dual MNK1/2 and PI3K/mTOR inhibiting hybrid agents was less effective at slowing cell migration.