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YB-1过表达通过激活Akt促进TGF-β1诱导的上皮-间质转化。

YB-1 overexpression promotes a TGF-β1-induced epithelial-mesenchymal transition via Akt activation.

作者信息

Ha Bin, Lee Eun Byul, Cui Jun, Kim Yosup, Jang Ho Hee

机构信息

Department of Molecular Medicine, Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon 406-799, Republic of Korea.

Department of Molecular Medicine, Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon 406-799, Republic of Korea; Gachon Medical Research Institute, Gil Medical Center, Gachon University, Incheon, Republic of Korea.

出版信息

Biochem Biophys Res Commun. 2015 Mar 6;458(2):347-51. doi: 10.1016/j.bbrc.2015.01.114. Epub 2015 Jan 30.

Abstract

The Y-box binding protein-1 (YB-1) is a transcription/translation regulatory protein, and the expression thereof is associated with cancer aggressiveness. In the present study, we explored the regulatory effects of YB-1 during the transforming growth factor-β1 (TGF-β1)-induced epithelial-to-mesenchymal transition (EMT) in lung adenocarcinoma cells. Downregulation of YB-1 increased E-cadherin promoter activity, and upregulation of YB-1 decreased promoter activity, suggesting that the YB-1 level may be correlated with the EMT. TGF-β1 induced YB-1 expression, and TGF-β1 translocated cytosolic YB-1 into the nucleus. YB-1 overexpression promoted TGF-β1-induced downregulation of epithelial markers, upregulation of mesenchymal markers, and cell migration. Moreover, YB-1 overexpression enhanced the expression of E-cadherin transcriptional repressors via TGF-β1-induced Akt activation. Our findings afford new insights into the role played by YB-1 in the TGF-β1 signaling pathway.

摘要

Y盒结合蛋白1(YB-1)是一种转录/翻译调节蛋白,其表达与癌症侵袭性相关。在本研究中,我们探讨了YB-1在转化生长因子-β1(TGF-β1)诱导的肺腺癌细胞上皮-间质转化(EMT)过程中的调节作用。YB-1的下调增加了E-钙黏蛋白启动子活性,而YB-1的上调则降低了启动子活性,这表明YB-1水平可能与EMT相关。TGF-β1诱导YB-1表达,并使胞质中的YB-1转位至细胞核。YB-1过表达促进了TGF-β1诱导的上皮标志物下调、间质标志物上调以及细胞迁移。此外,YB-1过表达通过TGF-β1诱导的Akt激活增强了E-钙黏蛋白转录抑制因子的表达。我们的研究结果为YB-1在TGF-β1信号通路中所起的作用提供了新的见解。

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