EWI-2 controls nucleocytoplasmic shuttling of EGFR signaling molecules and miRNA sorting in exosomes to inhibit prostate cancer cell metastasis.
EWI-2 controls nucleocytoplasmic shuttling of EGFR signaling molecules and miRNA sorting in exosomes to inhibit prostate cancer cell metastasis.
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DOI：
10.1002/1878-0261.12930
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发表时间：
2021-05
影响因子：
6.6
通讯作者：
Wei Q
中科院分区：
文献类型：
--
作者：
Fu C;Zhang Q;Wang A;Yang S;Jiang Y;Bai L;Wei Q
前列腺癌的早期和准确诊断是非常重要的，因为转移性前列腺癌仍然很难治疗。EWI-2是Ig蛋白亚家族的一员，被认为可以抑制PCa细胞的迁移。在本研究中，我们发现EWI-2定位于细胞膜和外体上，调节miR-3934-5p在细胞和外体之间的分布。有趣的是，我们观察到EWI-2不仅定位于质膜，还定位于核膜(核膜)，在那里它调节信号分子和miRNA的核转位。总之，在脂质双层中发现的EWI-2的这些功能似乎通过表皮生长因子受体-丝裂原活化蛋白激酶-细胞外信号调节激酶(EGFR-MAPK-ERK)途径来调节PCa细胞的转移。我们的研究为EWI-2在PCa转移中的分子功能提供了新的见解，并强调EWI-2是一个潜在的PCa生物标志物。我们的发现确定EWI-2是一个潜在的前列腺癌(PCA)生物标记物。EWI-2通过定位于脂质双层，促进EGFR信号分子的核质穿梭，调节外切体中microRNA的分选，参与了前列腺癌的转移。EWI-2的这些分子功能导致表皮生长因子受体-丝裂原活化蛋白激酶-细胞外信号调节激酶(EGFR-MAPK-ERK)信号通路下游激活，促进PCa细胞迁移。
Early and accurate diagnosis of prostate cancer (PCa) is extremely important, as metastatic PCa remains hard to treat. EWI‐2, a member of the Ig protein subfamily, is known to inhibit PCa cell migration. In this study, we found that EWI‐2 localized on both the cell membrane and exosomes regulates the distribution of miR‐3934‐5p between cells and exosomes. Interestingly, we observed that EWI‐2 is localized not only on the plasma membrane but also on the nuclear envelope (nuclear membrane), where it regulates the nuclear translocation of signaling molecules and miRNA. Collectively, these functions of EWI‐2 found in lipid bilayers appear to regulate PCa cell metastasis through the epidermal growth factor receptor‐mitogen‐activated protein kinase‐extracellular‐signal‐regulated kinase (EGFR‐MAPK‐ERK) pathway. Our research provides new insights into the molecular function of EWI‐2 on PCa metastasis, and highlights EWI‐2 as a potential PCa biomarker. Our findings identify EWI‐2 as a potential prostate cancer (PCa) biomarker. EWI‐2 is involved in PCa metastasis through its localization on lipid bilayers where it facilitates nucleocytoplasmic shuttling of EGFR signaling molecules and also regulates microRNA sorting in exosomes. These molecular functions of EWI‐2 result in downstream activation of the epidermal growth factor receptor‐mitogen‐activated protein kinase‐extracellular‐signal‐regulated kinase (EGFR‐MAPK‐ERK) signaling pathway and promote PCa cell migration.
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