Up-regulation of S100A16 expression promotes epithelial-mesenchymal transition via Notch1 pathway in breast cancer.
Up-regulation of S100A16 expression promotes epithelial-mesenchymal transition via Notch1 pathway in breast cancer.
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DOI：
10.1186/s12929-014-0097-8
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发表时间：
2014-10-07
影响因子：
11
通讯作者：
Wang S
中科院分区：
文献类型：
--
作者：
Zhou W;Pan H;Xia T;Xue J;Cheng L;Fan P;Zhang Y;Zhu W;Xue Y;Liu X;Ding Q;Liu Y;Wang S
我们之前的研究表明，S100A16 促进脂肪生成，并参与膳食钙诱导的体重增加衰减。迄今为止，S100A16在乳腺癌中的功能仍有待阐明。在这项研究中，我们观察到与配对的邻近非癌组织相比，S100A16 在人类乳腺癌组织中的表达水平更高。进一步检查表明，MCF-7细胞中S100A16的过表达可以增加细胞增殖和集落形成。一个主要的机制变化是S100A16能够上调转录因子Notch1、ZEB1和ZEB2，这些转录因子能够直接抑制上皮标记物E-钙粘蛋白和β-连环蛋白的表达，但增加间质标记物N-钙粘蛋白和波形蛋白，这是上皮-间质转化(EMT)的一种特征表型。除了形态学变化外，S100A16 过表达的 MCF-7 细胞的迁移和侵袭也增加。重要的是，通过特异性siRNA敲低Notch1可以逆转S100A16过表达诱导的EMT，这证实了Notch1在S100A16诱导的EMT过程中发挥着关键作用。总之，我们的数据表明S100A16具有调节某些胚胎转录因子以促进乳腺癌细胞EMT的潜在功能，这可能是乳腺癌治疗的重要靶位点。本文的在线版本 (doi:10.1186/s12929-014-0097-8) 包含补充材料，可供授权用户使用。
Our previous studies demonstrated that S100A16 promotes adipogenesis and is involved in weight gain attenuation induced by dietary calcium. Till now, the function of S100A16 in the breast cancer remains to be elucidated. In this study, we observed that S100A16 was expressed in higher levels in human breast cancer tissues compared with paired adjacent non-cancerous tissues. Further examination showed that overexpression of S100A16 in MCF-7 cells could increase cell proliferation and colony formation. One major mechanistic change was that S100A16 was able to up-regulate the transcription factors Notch1, ZEB1, and ZEB2, which had the capacities to directly repress the expression of epithelial markers E-cadherin and β-catenin but increase mesenchymal markers N-cadherin and vimentin, a characterized phenotype of epithelial-mensenchymal transition (EMT). In addition to display with morphologic change, migration and invasion were increased in S100A16 over-expressed MCF-7 cells. Importantly, knockdown of Notch1 by specific siRNA could reverse the EMT induced by S100A16 overexpression, which confirmed that Notch1 played a critical role in the process of EMT induced by S100A16. All together, our data indicated that S100A16 had a potential function to regulate some embryonic transcription factors to promote EMT in breast cancer cells which may be an important target site for the therapy of breast cancer. The online version of this article (doi:10.1186/s12929-014-0097-8) contains supplementary material, which is available to authorized users.
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影响因子：
21.3
作者：
Vincent, Theresa;Neve, Etienne P. A.;Johnson, Jill R.;Kukalev, Alexander;Rojo, Federico;Albanell, Joan;Pietras, Kristian;Virtanen, Ismo;Philipson, Lennart;Leopold, Philip L.;Crystal, Ronald G.;Garcia de Herreros, Antonio;Moustakas, Aristidis;Pettersson, Ralf F.;Fuxe, Jonas
通讯作者：
Fuxe, Jonas
影响因子：
11.2
作者：
Wang Z;Li Y;Kong D;Banerjee S;Ahmad A;Azmi AS;Ali S;Abbruzzese JL;Gallick GE;Sarkar FH
通讯作者：
Sarkar FH
影响因子：
--
作者：
Das S;Becker BN;Hoffmann FM;Mertz JE
通讯作者：
Mertz JE
影响因子：
5.4
作者：
Pan, Hong;Zhou, Wenbin;Wang, Shui
通讯作者：
Wang, Shui
影响因子：
4.8
作者：
Sturchler, Emmanuel;Cox, Jos A.;Heizmann, Claus W.
通讯作者：
Heizmann, Claus W.