Curcumin inhibits breast cancer stem cell migration by amplifying the E-cadherin/β-catenin negative feedback loop.
Curcumin inhibits breast cancer stem cell migration by amplifying the E-cadherin/β-catenin negative feedback loop.
复制标题
DOI：
10.1186/scrt506
复制
发表时间：
2014-10-14
影响因子：
7.5
通讯作者：
Das T
中科院分区：
文献类型：
--
作者：
Mukherjee S;Mazumdar M;Chakraborty S;Manna A;Saha S;Khan P;Bhattacharjee P;Guha D;Adhikary A;Mukhjerjee S;Das T
肿瘤干细胞（cancer stem cells，CSCs）的存在与肿瘤的发生、治疗抵抗、肿瘤复发、血管生成和转移有关。姜黄素是一种植物多酚，具有多种抗肿瘤作用，并已显示出靶向CSC。在这里，我们的目的是评估（i）乳腺CSC（bCSC）的迁移潜力恶化的潜在机制和（ii）姜黄素在调节其中的作用。通过细胞粘附、扩散、transwell迁移和三维侵袭试验评估MCF-7 bCSC的迁移行为。采用流式细胞术研究干细胞特性。姜黄素对bCSC的影响通过细胞活力测定、Western印迹、共聚焦显微镜和小干扰RNA（siRNA）介导的基因沉默来解释。采用免疫组化和流式细胞术对乳腺癌患者的样本进行评估。在这里，我们报告说，bCSC被赋予加重迁移性能，由于固有的抑制肿瘤抑制因子，E-钙粘蛋白，这是恢复姜黄素。对潜在机制的研究表明，在bCSC中，β-连环蛋白的较高核易位（i）减少E-钙粘蛋白/β-连环蛋白复合物形成和β-连环蛋白的膜保留，（ii）上调其上皮-间质转化（EMT）促进靶基因（包括Slug）的表达，从而（iii）下调E-钙粘蛋白转录，随后促进这些bCSC的EMT和迁移。相反，姜黄素抑制β-连环蛋白核转位，从而阻碍Slug的反式激活。因此，E-钙粘蛋白表达恢复，从而增加E-钙粘蛋白/β-连环蛋白复合物形成和更多β-连环蛋白的胞质保留，以最终抑制BCSC的EMT和迁移。累积起来，我们的研究结果揭示，姜黄素通过放大E-钙粘蛋白/β-连环蛋白负反馈环抑制bCSC迁移。本文的在线版本（doi：10.1186/dot 506）包含补充材料，可供授权用户使用。
The existence of cancer stem cells (CSCs) has been associated with tumor initiation, therapy resistance, tumor relapse, angiogenesis, and metastasis. Curcumin, a plant ployphenol, has several anti-tumor effects and has been shown to target CSCs. Here, we aimed at evaluating (i) the mechanisms underlying the aggravated migration potential of breast CSCs (bCSCs) and (ii) the effects of curcumin in modulating the same. The migratory behavior of MCF-7 bCSCs was assessed by using cell adhesion, spreading, transwell migration, and three-dimensional invasion assays. Stem cell characteristics were studied by using flow cytometry. The effects of curcumin on bCSCs were deciphered by cell viability assay, Western blotting, confocal microscopy, and small interfering RNA (siRNA)-mediated gene silencing. Evaluations of samples of patients with breast cancer were performed by using immunohistochemistry and flow cytometry. Here, we report that bCSCs are endowed with aggravated migration property due to the inherent suppression of the tumor suppressor, E-cadherin, which is restored by curcumin. A search for the underlying mechanism revealed that, in bCSCs, higher nuclear translocation of beta-catenin (i) decreases E-cadherin/beta-catenin complex formation and membrane retention of beta-catenin, (ii) upregulates the expression of its epithelial-mesenchymal transition (EMT)-promoting target genes (including Slug), and thereby (iii) downregulates E-cadherin transcription to subsequently promote EMT and migration of these bCSCs. In contrast, curcumin inhibits beta-catenin nuclear translocation, thus impeding trans-activation of Slug. As a consequence, E-cadherin expression is restored, thereby increasing E-cadherin/beta-catenin complex formation and cytosolic retention of more beta-catenin to finally suppress EMT and migration of bCSCs. Cumulatively, our findings disclose that curcumin inhibits bCSC migration by amplifying E-cadherin/beta-catenin negative feedback loop. The online version of this article (doi:10.1186/scrt506) contains supplementary material, which is available to authorized users.
登录
查看更多内容
影响因子：
10.5
作者：
Dontu, G;Abdallah, WM;Wicha, MS
通讯作者：
Wicha, MS
影响因子：
37.3
作者：
Chen L;Li M;Li Q;Wang CJ;Xie SQ
通讯作者：
Xie SQ
DOI：
10.1038/bonekey.2013.105
发表时间：
2013-07-03
期刊：
BoneKEy reports
影响因子：
--
作者：
Malanchi, Ilaria
通讯作者：
Malanchi, Ilaria
影响因子：
3.8
作者：
Kakarala, Madhuri;Brenner, Dean E.;Korkaya, Hasan;Cheng, Connie;Tazi, Karim;Ginestier, Christophe;Liu, Suling;Dontu, Gabriela;Wicha, Max S.
通讯作者：
Wicha, Max S.
使用新型姜黄素类似物 GO-Y030 靶向结肠癌干细胞
影响因子：
8.8
作者：
Lin, L.;Liu, Y.;Li, H.;Li, P-K;Fuchs, J.;Shibata, H.;Iwabuchi, Y.;Lin, J.
通讯作者：
Lin, J.