p53-R273H promotes cancer cell migration via upregulation of neuraminidase-1.
p53-R273H promotes cancer cell migration via upregulation of neuraminidase-1.
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p53-R273H 通过上调神经氨酸酶-1 促进癌细胞迁移
DOI：
10.7150/jca.44718
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发表时间：
2020
影响因子：
3.9
通讯作者：
Yi Y
中科院分区：
文献类型：
--
作者：
Lv T;Lv H;Fei J;Xie Y;Lian D;Hu J;Tang L;Shi X;Wang J;Zhang S;Li F;Jiang X;Yi Y
越来越多的证据表明热点p53突变体具有促进细胞迁移和肿瘤转移的功能获得性。然而，分子机制尚未完全理解。在这里，我们表明，热点突变，p53-R273 H，促进非小细胞肺癌（NSCLC）细胞迁移和上调神经氨酸酶-1（NEU 1），参与细胞增殖，细胞迁移和肿瘤发生的唾液酸酶的mRNA和蛋白质表达。NEU 1的沉默导致整合素β4的上调，其显著抑制由p53-R273 H诱导的NSCLC细胞迁移。机制上，p53-R273 H通过激活AKT信号传导促进NEU 1转录。重要的是，NEU 1表达在携带突变型p53的人NSCLC样品中上调，并且与不良临床结果相关。总之，这项研究强调了NEU 1在p53-R273 H诱导的NSCLC细胞迁移中的重要作用，并为NSCLC的诊断和治疗提供了潜在的靶点。
Accumulating evidence indicates that hotspot p53 mutants have gain-of-function in promoting cell migration and tumor metastasis. However, the molecular mechanisms are not completely understood. Here, we show that a hotspot mutation, p53-R273H, promotes non-small cell lung cancer (NSCLC) cell migration and upregulates the mRNA and protein expression of neuraminidase-1 (NEU1), a sialidase involved in cell proliferation, cell migration and tumorigenesis. Silencing of NEU1 leads to upregulation of integrin β4 which significantly inhibits NSCLC cell migration induced by p53-R273H. Mechanistically, p53-R273H promotes NEU1 transcription via activation of AKT signaling. Importantly, NEU1 expression is upregulated in human NSCLC samples harboring mutant p53 and is associated with poor clinical outcome. Overall, this study highlights an important role of NEU1 in p53-R273H-induced NSCLC cell migration and provides a potential target for NSCLC diagnosis and treatment.