Department of Breast Surgery, Shandong University School of Medicine, Jinan, Shandong, China.
Cancer Sci. 2011 Jun;102(6):1151-7. doi: 10.1111/j.1349-7006.2011.01919.x. Epub 2011 Apr 5.
The epithelial-mesenchymal transition (EMT) is a process in which polarized epithelial cells are converted into motile mesenchymal cells. During cancer development, EMT is conducive to tumor dissemination and metastatic spread. While overexpression of metadherin (MTDH) in breast cancer cell lines and tissues has been found to be associated with aggressive tumor behavior, its precise role in invasion and metastasis is largely unknown. Here we report that MTDH overexpression could significantly enhance the invasion and migration of breast cancer cells by inducing EMT. Metadherin overexpression led to upregulation of mesenchymal marker fibronectin, downregulation of epithelial marker E-cadherin, and the nuclear accumulation of beta-catenin. Also, transcription factors Snail and Slug were upregulated in breast cancer cells overexpressing MTDH. Overexpression of MTDH enhanced the invasiveness and migration ability of breast cancer cells in vitro. In addition, overexpression of MTDH led to increased acquisition of CD44(+) /CD24(-/low) markers that are characteristic of breast cancer stem cells. We also showed that NF-kappa was involved in the expression of EMT-related markers. Taken together, our results suggest that MTDH could promote EMT in breast cancer cells in driving the progression of their aggressive behavior.
上皮-间充质转化（EMT）是一种极性上皮细胞转化为运动性间充质细胞的过程。在癌症发展过程中，EMT 有利于肿瘤的扩散和转移。虽然在乳腺癌细胞系和组织中发现 metadherin（MTDH）的过表达与侵袭性肿瘤行为相关，但它在侵袭和转移中的确切作用在很大程度上仍是未知的。在这里，我们报告 MTDH 的过表达可以通过诱导 EMT 显著增强乳腺癌细胞的侵袭和迁移。MTDH 的过表达导致间充质标志物纤维连接蛋白上调，上皮标志物 E-钙黏蛋白下调，以及β-连环蛋白的核积累。此外，在过表达 MTDH 的乳腺癌细胞中转录因子 Snail 和 Slug 上调。MTDH 的过表达增强了乳腺癌细胞在体外的侵袭和迁移能力。此外，MTDH 的过表达导致 CD44(+) / CD24(-/low)标志物的获得增加，这些标志物是乳腺癌干细胞的特征。我们还表明，NF-kappa 参与 EMT 相关标志物的表达。总之，我们的结果表明，MTDH 可以促进乳腺癌细胞中的 EMT，从而推动其侵袭性行为的进展。
