Shen Hui, Qin Haihong, Guo Junsheng
Department of Military Hygiene, Second Military Medical University, Shanghai 200433, PR China.
Mol Biol Rep. 2009 Apr;36(4):653-9. doi: 10.1007/s11033-008-9225-4. Epub 2008 Mar 11.
The recent report highlighted a significant association between signal transducer and activator of transcription 3 (STAT3) and Snail and LIV-1 (SLC39A6 or ZIP6), the breast cancer-associated protein that belongs to a new subfamily of zinc transporters. LIV-1 is a downstream target of STAT3, both in zebrafish and mammalian cells and provides control over epithelial-mesenchymal transition (EMT). Crucially, these observations link LIV-1, previously demonstrated to be associated with lymph node metastasis in breast cancer, to genes with a proven role in development. A putative role of LIV-1 as a regulator of E-cadherin that modulates the cell-cell adhesion is thus inferred. In present study, the correlation of LIV-1 and E-cadherin expression in human breast cancer cell MCF-7 and the effect of LIV-1 expression on the cell growth were assessed to explore the possible mechanisms associated with this observation in breast cancer. It was shown that the silencing of LIV-1 would induce the down-expression of E-cadherin. There was opposite results if the cells were overexpressed with LIV-1. In addition, the results showed that promotion effect after silencing of LIV-1 and inhibition effect after overexpression of LIV-1 in transfected cells. To our knowledge, this is the first evidence that the expression of E-cadherin could be regulated by the zinc transporter LIV-1. The results suggest that there is an association of LIV-1 expression with less aggressive tumors due to high E-cadherin expression because of high LIV-1 expression. LIV-1 may be a regulator of E-cadherin.
最近的一份报告强调了信号转导和转录激活因子3（STAT3）与Snail和LIV-1（SLC39A6或ZIP6）之间的显著关联，LIV-1是一种与乳腺癌相关的蛋白质，属于锌转运蛋白新亚家族。在斑马鱼和哺乳动物细胞中，LIV-1都是STAT3的下游靶点，并对上皮-间质转化（EMT）起控制作用。至关重要的是，这些观察结果将先前已证明与乳腺癌淋巴结转移相关的LIV-1与在发育过程中具有已证实作用的基因联系起来。因此推断LIV-1作为E-钙黏蛋白调节剂的假定作用，该调节剂可调节细胞间黏附。在本研究中，评估了人乳腺癌细胞MCF-7中LIV-1和E-钙黏蛋白表达的相关性以及LIV-1表达对细胞生长的影响，以探索与乳腺癌中这一观察结果相关的可能机制。结果表明，LIV-1沉默会诱导E-钙黏蛋白的表达下调。如果细胞过表达LIV-1，则结果相反。此外，结果表明，转染细胞中LIV-1沉默后有促进作用，过表达LIV-1后有抑制作用。据我们所知，这是E-钙黏蛋白表达可由锌转运蛋白LIV-1调节的首个证据。结果表明，由于LIV-1高表达导致E-钙黏蛋白高表达，LIV-1表达与侵袭性较小的肿瘤有关。LIV-1可能是E-钙黏蛋白的调节剂。
