The linker of nucleoskeleton and cytoskeleton complex is required for X-ray-induced epithelial-mesenchymal transition.
The linker of nucleoskeleton and cytoskeleton complex is required for X-ray-induced epithelial-mesenchymal transition.
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DOI：
10.1093/jrr/rrac104
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发表时间：
2023-03-23
影响因子：
2
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中科院分区：
文献类型：
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核骨架与细胞骨架连接体（LINC）复合物参与了核膜的多种功能，包括核迁移、机械转导和DNA修复。我们先前揭示了LINC复合物组分Sad 1和UNC 84结构域包含1（SUN 1）是亚致死剂量X射线增强细胞迁移和侵袭所必需的。本研究的重点是上皮间质转化（EMT），这有助于细胞迁移。因此，本研究旨在研究亚致死剂量X射线照射是否诱导EMT以及LINC复合物组分SUN 1是否参与低剂量X射线诱导的EMT。本研究表明，低剂量（0.5戈伊或2戈伊）X射线照射诱导人乳腺癌MDA-MB-231细胞EMT。此外，X射线照射增加了SUN 1的表达。因此，使用siRNA耗尽SUN 1。在SUN 1缺失的细胞中，低剂量X射线照射不会诱导EMT。此外，尽管SUN 1剪接变体SUN1_916-耗尽的细胞（含有SUN 1的916个氨基酸[AA]）像未转染的对照细胞一样被低剂量X-照射诱导EMT，但SUN1_888-耗尽的细胞（其编码888个AA）不被低剂量X-照射诱导EMT。此外，由于Wnt/β-连环蛋白信号通路通过E-钙粘蛋白抑制子Snail的表达来调节E-钙粘蛋白的表达，因此检查了X射线照射后β-连环蛋白的表达。照射24小时后，在未转染的细胞或SUN1_916耗尽的细胞中β-连环蛋白表达增加，而在SUN 1或SUN1_888耗尽的细胞中β-连环蛋白表达保持不变且不增加。因此，在本研究中，我们发现低剂量X射线照射诱导EMT，而LINC复合物组分SUN 1，特别是SUN1_888，通过激活Wnt/β-catenin信号通路是X射线诱导EMT所必需的。
The linker of nucleoskeleton and cytoskeleton (LINC) complex has been implicated in various functions of the nuclear envelope, including nuclear migration, mechanotransduction and DNA repair. We previously revealed that the LINC complex component Sad1 and UNC84 domain containing 1 (SUN1) is required for sublethal-dose X-ray-enhanced cell migration and invasion. This study focused on epithelial-mesenchymal transition (EMT), which contributes to cell migration. Hence, the present study aimed to examine whether sublethal-dose X-irradiation induces EMT and whether LINC complex component SUN1 is involved in low-dose X-ray-induced EMT. This study showed that low-dose (0.5 Gy or 2 Gy) X-irradiation induced EMT in human breast cancer MDA-MB-231 cells. Additionally, X-irradiation increased the expression of SUN1. Therefore, SUN1 was depleted using siRNA. In SUN1-depleted cells, low-dose X-irradiation did not induce EMT. In addition, although the SUN1 splicing variant SUN1_916-depleted cells (containing 916 amino acids [AA] of SUN1) were induced EMT by low-dose X-irradiation like as non-transfected control cells, SUN1_888-depleted cells (which encodes 888 AA) were not induced EMT by low-dose X-irradiation. Moreover, since the Wnt/β-catenin signaling pathway regulates E-cadherin expression via the expression of the E-cadherin repressor Snail, the expression of β-catenin after X-irradiation was examined. After 24 hours of irradiation, β-catenin expression increased in non-transfected cells or SUN1_916-depleted cells, whereas β-catenin expression remained unchanged and did not increase in SUN1- or SUN1_888-depleted cells. Therefore, in this study, we found that low-dose X-irradiation induces EMT, and LINC complex component SUN1, especially SUN1_888, is required for X-ray-induced EMT via activation of the Wnt/β-catenin signaling pathway.
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DOI：
10.1083/jcb.201908036
发表时间：
2020-10-05
期刊：
The Journal of cell biology
影响因子：
--
作者：
Déjardin T;Carollo PS;Sipieter F;Davidson PM;Seiler C;Cuvelier D;Cadot B;Sykes C;Gomes ER;Borghi N
通讯作者：
Borghi N
影响因子：
5.7
作者：
Imaizumi H;Sato K;Nishihara A;Minami K;Koizumi M;Matsuura N;Hieda M
通讯作者：
Hieda M
影响因子：
6.2
作者：
Delaney, G;Jacob, S;Barton, M
通讯作者：
Barton, M
影响因子：
8.4
作者：
Jung, Jae-Won;Hwang, So-Young;Han, Inn-Oc
通讯作者：
Han, Inn-Oc
影响因子：
3.7
作者：
He E;Pan F;Li G;Li J
通讯作者：
Li J