Škalamera Dubravka, Dahmer-Heath Mareike, Stevenson Alexander J, Pinto Cletus, Shah Esha T, Daignault Sheena M, Said Nur Akmarina B M, Davis Melissa, Haass Nikolas K, Williams Elizabeth D, Hollier Brett G, Thompson Erik W, Gabrielli Brian, Gonda Thomas J
University of Queensland Diamantina Institute, University of Queensland, Translational Research Institute, Brisbane, QLD, Australia.
Mater Medical Research Institute, The University of Queensland, Translational Research Institute, Woolloongabba, Australia.
Oncotarget. 2016 Sep 20;7(38):61000-61020. doi: 10.18632/oncotarget.11314.
Epithelial to mesenchymal transition (EMT) is a developmental program that has been implicated in progression, metastasis and therapeutic resistance of some carcinomas. To identify genes whose overexpression drives EMT, we screened a lentiviral expression library of 17000 human open reading frames (ORFs) using high-content imaging to quantitate cytoplasmic vimentin. Hits capable of increasing vimentin in the mammary carcinoma-derived cell line MDA-MB-468 were confirmed in the non-tumorigenic breast-epithelial cell line MCF10A. When overexpressed in this model, they increased the rate of cell invasion through Matrigel™, induced mesenchymal marker expression and reduced expression of the epithelial marker E-cadherin. In gene-expression datasets derived from breast cancer patients, the expression of several novel genes correlated with expression of known EMT marker genes, indicating their in vivo relevance. As EMT-associated properties are thought to contribute in several ways to cancer progression, genes identified in this study may represent novel targets for anti-cancer therapy.
上皮-间质转化（EMT）是一种发育程序，与某些癌症的进展、转移和治疗抗性有关。为了鉴定那些过表达驱动EMT的基因，我们使用高内涵成像技术对17000个人类开放阅读框（ORF）的慢病毒表达文库进行筛选，以定量细胞质波形蛋白。在非致瘤性乳腺上皮细胞系MCF10A中证实了能够增加乳腺癌衍生细胞系MDA-MB-468中波形蛋白的命中基因。当在该模型中过表达时，它们增加了细胞通过基质胶™的侵袭率，诱导了间充质标志物的表达，并降低了上皮标志物E-钙黏蛋白的表达。在源自乳腺癌患者的基因表达数据集中，几个新基因的表达与已知EMT标志物基因的表达相关，表明它们在体内具有相关性。由于EMT相关特性被认为以多种方式促进癌症进展，本研究中鉴定的基因可能代表抗癌治疗的新靶点。
