Serine 207 phosphorylated lysyl-tRNA synthetase predicts disease-free survival of non-small-cell lung carcinoma.
Serine 207 phosphorylated lysyl-tRNA synthetase predicts disease-free survival of non-small-cell lung carcinoma.
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DOI：
10.18632/oncotarget.18053
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发表时间：
2017-09-12
期刊：
影响因子：
--
通讯作者：
Razin E
中科院分区：
文献类型：
--
作者：
Boulos S;Park MC;Zeibak M;Foo SY;Jeon YK;Kim YT;Motzik A;Tshori S;Hamburger T;Kim S;Nechushtan H;Razin E
已经表明，各种tRNA合成酶表现出与它们在翻译中的原始作用无关的非规范活性。我们先前已经描述了一种信号转导途径，其中丝氨酸207磷酸化赖氨酰-tRNA合成酶（P-s207 LysRS）从细胞质多tRNA合成酶复合物（MSC）释放到细胞核中，在细胞核中它激活刺激的培养肥大细胞和心肌细胞中的转录因子MITF。在这里，我们描述了一个类似的转换LysRS由于EGFR信号激活在人肺癌。我们的数据显示EGFR的激活导致LysRS在丝氨酸207位的磷酸化，其从MSC释放并易位到细胞核。然后，我们制备了P-s207 LysRS兔多克隆抗体，并测试了242个来自非小细胞肺癌患者的组织微阵列样本。与WT EGFR患者相比，在EGFR突变患者中观察到P-s207 LysRS的高度阳性核染色，并与平均无病生存期（DFS）改善相关。此外，当P-s207 LysRS存在于细胞核中时，EGFR突变和淋巴结转移阴性的患者具有更好的DFS。所呈现的数据强烈表明P-s207 LysRS在非小细胞肺癌中的功能和预后意义。
It has been shown that various tRNA synthetases exhibit non-canonical activities unrelated to their original role in translation. We have previously described a signal transduction pathway in which serine 207 phosphorylated lysyl-tRNA synthetase (P-s207 LysRS) is released from the cytoplasmic multi-tRNA synthetase complex (MSC) into the nucleus, where it activates the transcription factor MITF in stimulated cultured mast cells and cardiomyocytes. Here we describe a similar transformation of LysRS due to EGFR signaling activation in human lung cancer. Our data shows that activation of the EGFR results in phosphorylation of LysRS at position serine 207, its release from the MSC and translocation to the nucleus. We then generated a P-s207 LysRS rabbit polyclonalantibody and tested 242 tissue micro-array samples derived from non-small-cell lung cancer patients. Highly positive nuclear staining for P-s207 LysRS was noted in patients with EGFR mutations as compared to WT EGFR patients and was associated with improved mean disease-free survival (DFS). In addition, patients with mutated EGFR and negative lymph node metastases had better DFS when P-s207 LysRS was present in the nucleus. The data presented strongly suggests functional and prognostic significance of P-s207 LysRS in non-small-cell lung cancer.
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