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沉默 SOX2 诱导间充质-上皮转化,其表达预测 CRC 患者肝和淋巴结转移。

Silencing SOX2 induced mesenchymal-epithelial transition and its expression predicts liver and lymph node metastasis of CRC patients.

机构信息

Systems Biology Division, Zhejiang-California International Nanosystems Institute, Zhejiang University, Hangzhou, Zhejiang, China.

出版信息

PLoS One. 2012;7(8):e41335. doi: 10.1371/journal.pone.0041335. Epub 2012 Aug 17.

Abstract

SOX2 is an important stem cell marker and plays important roles in development and carcinogenesis. However, the role of SOX2 in Epithelial-Mesenchymal Transition has not been investigated. We demonstrated, for the first time, that SOX2 is involved in the Epithelial-Mesenchymal Transition (EMT) process as knock downof SOX2 in colorectal cancer (CRC) SW620 cells induced a Mesenchymal-Epithelial Transition (MET) process with recognized changes in the expression of key genes involved in the EMT process including E-cadherin and vimentin. In addition, we provided a link between SOX2 activity and the WNT pathway by showing that knock down of SOX2 reduced the WNT pathway activity in colorectal cancer (CRC) cells. We further demonstrated that SOX2 is involved in cell migration and invasion in vitro and in metastasis in vivo for CRC cells, and that the process might be mediated through the MMP2 activity. Finally, an IHC analysis of 44 cases of colorectal cancer patients suggested that SOX2 is a prognosis marker for metastasis of colorectal cancers.

摘要

SOX2 是一种重要的干细胞标志物,在发育和肿瘤发生中发挥重要作用。然而,SOX2 在上皮-间充质转化中的作用尚未得到研究。我们首次证明,SOX2 参与上皮-间充质转化(EMT)过程,因为敲低结直肠癌细胞(CRC)SW620 中的 SOX2 诱导了间充质-上皮转化(MET)过程,其中涉及 EMT 过程的关键基因的表达发生了公认的变化,包括 E-钙黏蛋白和波形蛋白。此外,我们通过显示敲低 SOX2 降低了结直肠癌细胞(CRC)中的 WNT 途径活性,提供了 SOX2 活性与 WNT 途径之间的联系。我们进一步证明,SOX2 参与了结直肠癌细胞的体外迁移和侵袭以及体内转移,并通过 MMP2 活性介导该过程。最后,对 44 例结直肠癌患者的 IHC 分析表明,SOX2 是结直肠癌转移的预后标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd57/3422347/3c35526652ad/pone.0041335.g001.jpg

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