Stanniocalicin 2 suppresses breast cancer cell migration and invasion via the PKC/claudin-1-mediated signaling.
Stanniocalicin 2 suppresses breast cancer cell migration and invasion via the PKC/claudin-1-mediated signaling.
复制标题
Stanniocalicin 2 通过 PKC/claudin-1 介导的信号传导抑制乳腺癌细胞迁移和侵袭。
DOI：
10.1371/journal.pone.0122179
复制
发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Yang G
中科院分区：
文献类型：
--
作者：
Hou J;Wang Z;Xu H;Yang L;Yu X;Yang Z;Deng Y;Meng J;Feng Y;Guo X;Yang G
斯坦钙素（STC）是一种糖蛋白激素，在多种组织中表达，调节Ca2+和PO4-稳态。STC2是STC家族的一员，据报道与肿瘤发生有关。在这项研究中，我们研究了STC2的表达是否与乳腺癌细胞的迁移和侵袭有关。我们发现转染STC2 shRNA的乳腺癌细胞系231 HM表现出高运动性，成纤维细胞形态，细胞迁移和侵袭增强。231个细胞中STC2的引入减少了细胞的迁移和侵袭。与对照细胞相比，231个HM细胞中STC2的沉默减少了细胞凋亡，而231个细胞中STC2的过表达促进了细胞凋亡。机制研究表明，STC2负调控PKC，控制Claudin-1的表达，进而诱导emt相关因子ZEB1、ZO-1、Slug、Twist、MMP9的表达。使用PKC抑制剂（Go 6983）抑制PKC活性可以恢复stc2沉默细胞的正常运动。此外，体内动物实验表明，STC2抑制乳腺癌细胞的肿瘤发生和转移。综上所述，这些结果表明STC2可能至少部分地通过PKC/ cludin -1介导的人类乳腺癌细胞信号传导抑制EMT。因此，STC2可能被用作人类乳腺癌转移和靶向治疗的生物标志物。
Stanniocalcin (STC), a glycoprotein hormone, is expressed in a wide variety of tissues to regulate Ca2+ and PO4- homeostasis. STC2, a member of STC family, has been reported to be associated with tumor development. In this study, we investigated whether the expression of STC2 is associated with migration and invasion of breast cancer cells. We found that breast cancer cell line 231 HM transfected with STC2 shRNA displayed high motility, fibroblast morphology, and enhanced cell migration and invasion. Introduction of STC2 in 231 cells reduced cell migration and invasion. In response to irradiation, silencing of STC2 in 231 HM cells reduced apoptosis, whereas overexpression of STC2 in 231 cells promoted apoptosis, compared with in control cells. Mechanistic study showed that STC2 negatively regulated PKC to control the expression of Claudin-1, which subsequently induced the expressions of EMT-related factors including ZEB1, ZO-1, Slug, Twist, and MMP9. Suppression of PKC activity by using a PKC inhibitor (Go 6983) restored the normal motility of STC2-silenced cells. Furthermore, in vivo animal assay showed that STC2 inhibited tumorigenesis and metastasis of breast cancer cells. Collectively, these results indicate that STC2 may inhibit EMT at least partially through the PKC/Claudin-1-mediated signaling in human breast cancer cells. Thus, STC2 may be exploited as a biomarker for metastasis and targeted therapy in human breast cancer.
登录
查看更多内容
影响因子：
5.7
作者：
Tamura, Kenji;Furihata, Mutsuo;Nakagawa, Hidewaki
通讯作者：
Nakagawa, Hidewaki
鉴定过氧蛋白6在乳腺癌进展中的功能作用。
DOI：
10.1186/bcr1789
发表时间：
2007
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Chang XZ;Li DQ;Hou YF;Wu J;Lu JS;Di GH;Jin W;Ou ZL;Shen ZZ;Shao ZM
通讯作者：
Shao ZM
DOI：
10.1152/ajpendo.00268.2004
发表时间：
2005-01-01
影响因子：
5.1
作者：
Gagliardi, AD;Kuo, EYW;DiMattia, GE
通讯作者：
DiMattia, GE
影响因子：
6.4
作者：
Volland, Sonja;Kugler, Wilfried;Becker, Juergen
通讯作者：
Becker, Juergen
影响因子：
5.3
作者：
Ito, D;Walker, JR;Thinakaran, G
通讯作者：
Thinakaran, G