PDF(Pubmed)
Abstract：
Breast cancer is a common tumor type among women, with a high fatality due to metastasis. Metastasis suppressors encode proteins that inhibit the metastatic cascade independent of the primary tumor growth. Raf kinase inhibitory protein (RKIP) is one of the promising metastasis suppressor candidates. RKIP is reduced or lost in aggressive variants of different types of cancer. A few pre-clinical or clinical studies have capitalized on this protein as a possible therapeutic target. In this article, we employed two breast cancer cells to highlight the role of RKIP as an antimetastatic gene. One is the low metastatic MCF-7 with high RKIP expression, and the other is MDA-MB-231 highly metastatic cell with low RKIP expression. We used high-throughput data to explore how RKIP is lost in human tissues and its effect on cell mobility. Based on our previous work recapitulating the links between RKIP and SNAI, we experimentally manipulated RKIP in the cell models through its novel upstream NME1 and investigated the subsequent genotypic and phenotypic changes. We also demonstrated that RKIP explained the uneven migration abilities of the two cell types. Furthermore, we identified the regulatory circuit that might carry the effect of an existing drug, Epirubicin, on activating gene transcription. In conclusion, we propose and test a potential strategy to reverse the metastatic capability of breast cancer cells by chemically manipulating RKIP expression.
摘要：
乳腺癌是女性常见的肿瘤类型，转移导致的死亡率很高。转移抑制因子编码不依赖于原发肿瘤生长而抑制转移级联的蛋白质。Raf激酶抑制蛋白（RKIP）是有前途的转移抑制因子之一。RKIP在不同类型癌症的侵袭性变体中降低或丢失。一些临床前或临床研究已经利用该蛋白质作为可能的治疗靶标。在这篇文章中,我们使用两种乳腺癌细胞来强调RKIP作为抗转移基因的作用.一种是具有高RKIP表达的低转移性MCF-7，另一种是MDA-MB-231高转移细胞，RKIP低表达。我们使用高通量数据来探索RKIP如何在人体组织中丢失及其对细胞移动性的影响。根据我们以前的工作，概述了RKIP和SNAI之间的联系，我们通过新的上游NME1对细胞模型中的RKIP进行了实验操作，并研究了随后的基因型和表型变化。我们还证明了RKIP解释了两种细胞类型的不均匀迁移能力。此外，我们确定了可能具有现有药物作用的调节回路，表阿霉素,激活基因转录。总之,我们提出并测试了一种通过化学操纵RKIP表达逆转乳腺癌细胞转移能力的潜在策略.
