Lamin A/C might be involved in the EMT signalling pathway

Lamin A/C might be involved in the EMT signalling pathway
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Lamin A/C 可能参与 EMT 信号通路

DOI:
10.1016/j.gene.2018.04.040
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发表时间:
2018
期刊:
影响因子:
3.5
通讯作者:
Kong Lu
Kong Lu
中科院分区:
生物学3区
文献类型:
--
作者:
Zuo Lingkun;Zhao Huanying;Yang Ronghui;Wang Liyong;Ma Hui;Xu Xiaoxue;Zhou Ping;Kong Lu

文献摘要

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我们之前报道过低和高格里森评分 (GS) 前列腺癌 (PC) 组织中核膜蛋白核纤层蛋白 A/C 的异质表达模式,现在我们发现这种变化与 LMNA 突变无关。这种表达模式似乎与上皮到间质转化(EMT)或间质到上皮转化(MET)的过程相似。核纤层蛋白 A/C 在 PC 的 EMT 或 MET 中的作用仍不清楚。因此,我们首先研究了不同GS值的PC组织和具有不同侵袭能力的不同细胞系中核纤层蛋白A/C与几种常见EMT标志物(例如E-cadherin、N-cadherin、β-catenin、snail、slug和vimentin)的表达水平及其关联性。我们的结果表明,核纤层蛋白 A/C 可能构成一种上皮标记物,可以更好地表示 PC 组织中的 EMT 和 MET,因为 GS 4+5 病例中核纤层蛋白 A/C 表达的减少可能与 EMT 过程相关,而 GS 5+4 病例中核纤层蛋白 A/C 的重新表达可能与 MET 相关。详细的 GS 更好地展示了核纤层蛋白 A/C 的变化和检查的 EMT 标记。 Lamin A/C 过表达或敲低通过直接调节 β-连环蛋白对细胞模型中的 EMT 生物标志物产生影响。因此,我们认为核纤层蛋白 A/C 可能作为区分 PC 细胞分化的可靠上皮生物标志物,也可能是 PC 中 EMT 或 MET 发生的基本因素。
We have previously reported a heterogeneous expression pattern of the nuclear membrane protein lamin A/C in low- and high-Gleason score (GS) prostate cancer (PC) tissues, and we have now found that this change is not associated with LMNA mutations. This expression pattern appears to be similar to the process of epithelial to mesenchymal transition (EMT) or to that of mesenchymal to epithelial transition (MET). The role of lamin A/C in EMT or MET in PC remains unclear. Therefore, we first investigated the expression levels of and the associations between lamin A/C and several common EMT markers, such as E-cadherin, N-cadherin, β-catenin, snail, slug and vimentin in PC tissues with different GS values and in different cell lines with varying invasion abilities. Our results suggest that lamin A/C might constitute a type of epithelial marker that better signifies EMT and MET in PC tissue, since a decrease in lamin A/C expression in GS 4 + 5 cases is likely associated with the EMT process, while the re-expression of lamin A/C in GS 5 + 4 cases is likely linked with MET. The detailed GS better exhibited the changes in lamin A/C and the EMT markers examined. Lamin A/C overexpression or knockdown had an impact on EMT biomarkers in a cell model by direct regulation of β-catenin. Hence, we suggest that lamin A/C might serve as a reliable epithelial biomarker for the distinction of PC cell differentiation and might also be a fundamental factor in the occurrence of EMT or MET in PC.