PRL-3 Promotes the Malignant Progression of Melanoma via Triggering Dephosphorylation and Cytoplasmic Localization of NHERF1
PRL-3 Promotes the Malignant Progression of Melanoma via Triggering Dephosphorylation and Cytoplasmic Localization of NHERF1
复制标题
PRL-3通过触发NHERF1的去磷酸化和细胞质定位促进黑色素瘤的恶性进展
DOI：
10.1038/jid.2015.154
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发表时间：
2015-09-01
影响因子：
6.5
通讯作者：
Xu, Qiang
中科院分区：
文献类型：
--
作者：
Fang, Xian-Ying;Song, Ran;Xu, Qiang
据报道，再生肝磷酸酶-3（PRL-3）在癌症的转移进展中具有关键作用。在这里，我们研究PRL-3如何增加黑色素瘤细胞的恶性程度。PRL-3在黑色素瘤恶性进展过程中表达逐渐增加。Akt的磷酸化在高度恶性的黑色素瘤细胞中升高，这伴随着核磷酸酶和张力蛋白同源物（PTEN）的减少。NHERF 1在丝氨酸位点的磷酸化受PRL-3调节，在去磷酸化后显示胞质易位，这导致核中PTEN的减少。在黑色素瘤细胞恶性进展过程中，观察到NHERF 1和PTEN从细胞核到细胞质的共易位。在接种到小鼠中之前，在B16 BL 6细胞中敲低细胞质NHERF 1后，肿瘤生长被显著抑制，并且存活时间延长。总之，据我们所知，以前未报道，我们已经确定NHERF 1作为PRL-3的潜在底物。其磷酸化状态以及其在细胞定位中的变化和与PTEN的关联与黑色素瘤的恶性进展相关。我们的数据为PRL-3如何促进黑色素瘤的恶性进展以及恶性黑色素瘤的诊断标志物或治疗靶点提供了解释。
Phosphatase of regenerating liver-3 (PRL-3) has been reported to have a critical role in metastatic progression of cancers. Here, we investigate how PRL-3 increases the malignant degree of melanoma cells. The expression of PRL-3 increased gradually during the malignant progression of melanoma. The phosphorylation of Akt was elevated in highly malignant melanoma cells, which was accompanied by a decrease in nuclear phosphatase and tensin homolog (PTEN). The phosphorylation of NHERF1 in the serine site was regulated by PRL-3 and showed cytoplasmic translocation upon dephosphorylation, which resulted in a decrease in nuclear PTEN. The co-translocation of NHERF1 and PTEN from the nucleus to the cytoplasm was observed during the malignant progression of melanoma cells. Tumor growth was inhibited significantly, and the survival was prolonged upon knockdown of cytoplasmic NHERF1 in B16BL6 cells prior to the inoculation into mice. Taken together, to our knowledge previously unreported, we have identified NHERF1 as a potential substrate of PRL-3. Its phosphorylation status as well as its change in cellular localization and association with PTEN correlated with the malignant progression of melanoma. Our data provide an explanation for how PRL-3 promotes the malignant progression of melanoma, as well as a diagnostic marker or therapeutic target for malignant melanoma.