The oncoprotein HBXIP enhances migration of breast cancer cells through increasing filopodia formation involving MEKK2/ERK1/2/Capn4 signaling
The oncoprotein HBXIP enhances migration of breast cancer cells through increasing filopodia formation involving MEKK2/ERK1/2/Capn4 signaling
复制标题
癌蛋白 HBXIP 通过增加涉及 MEKK2/ERK1/2/Capn4 信号传导的丝状伪足形成来增强乳腺癌细胞的迁移
DOI：
10.1016/j.canlet.2014.09.047
复制
发表时间：
2014-12-28
期刊：
影响因子：
9.7
通讯作者：
Ye, Lihong
中科院分区：
文献类型：
--
作者：
Li, Yinghui;Zhang, Zhao;Ye, Lihong
我们已经报道了癌蛋白HBXIP在促进乳腺癌细胞迁移中起着至关重要的作用。片状脂膜和丝足突起在肿瘤转移过程中起重要作用，涉及细胞骨架的动态重组。在此，我们观察到HBXIP和钙蛋白酶小亚基1(Capn4)在乳腺肿瘤临床转移淋巴结中的表达水平都很高。随后，我们发现HBXIP能够通过激活ERK1/2在启动子、mRNA和蛋白水平上调乳腺癌细胞中的Capn4。此外，我们还发现HBXIP通过上调MEKK2来激活ERK1/2。在功能上，我们发现HBXIP通过Capn4促进丝状足的形成，导致细胞迁移。因此，我们得出结论，癌蛋白HBXIP通过增加涉及MEKK2/ERK1/2/Capn4信号转导的丝状足形成来促进乳腺癌的转移。在治疗方面，HBXIP可能成为乳腺癌治疗的新靶点。(C)2014爱思唯尔爱尔兰有限公司。保留所有权利。
We have reported that the oncoprotein hepatitis B X-interacting protein (HBXIP) plays a crucial role in the promotion of migration of breast cancer cells. Lamellipodia and filopodia protrusions play fundamental roles, involving dynamic cytoskeleton reorganization in the metastasis of cancer. Here, we observed that the expression levels of both HBXIP and Calpain small subunit 1 (Capn4) were very high in clinical metastatic lymph nodes of breast tumor. Then, we found that HBXIP was able to up-regulate Capn4 at the levels of promoter, mRNA and protein in breast cancer cells through activation of ERK1/2. Moreover, we showed that HBXIP activated ERK1/2 through up-regulating MEKK2. In function, we revealed that HBXIP increased the filopodia formation through Capn4, resulting in cell migration. Thus, we conclude that the oncoprotein HBXIP enhances the migration of breast cancer through increasing filopodia formation involving MEKK2/ERK1/2/Capn4 signaling. Therapeutically, HBXIP may serve as a novel target in breast cancer. (C) 2014 Elsevier Ireland Ltd. All rights reserved.