Abstract 967: N-Myc interactor, a novel regulator of EMT

Abstract

Abstract Dissemination of tumor cells and subsequent colonization at distant sites is the most lethal event in cancer progression. The epithelial-mesenchymal transition (EMT) has recently been recognized as a foremost phenomenon underlying such events. Because of the importance of EMT, it is vital to understand what triggers it, as well as the mechanisms by which it is regulated. We have shown that N-myc interactor (NMI) plays a role in restricting malignant activities of cancerous cell lines in vivo and in vitro. This study describes a novel function of NMI in reducing the mesenchymal phenotype of breast cancer cell lines. Constitutive expression of NMI in the mesenchymal cell line MDA-MB-435, showed remarkable morphologic transition towards an epithelial appearance, accompanied by reduction or loss of several mesenchymal markers such as TWIST, MMP2, SNAI2 and ZEB1 and gain of epithelial markers such as E-cadherin and Keratin 18. Conversely, silencing NMI from immortalized breast epithelial line MCF10A, renders the cells more mesenchymal in appearance. Studies using a variety of additional cell lines consistently revealed that silencing of NMI expression coincided with increased expression of both ZEB1 and SNAI2, while NMI overexpression brought about decreased expression of ZEB1 and SNAI2. Assessment of NMI in breast cancer specimens revealed a significant loss of NMI transcript with increasing grade of breast cancer. Thus, overall, our data strongly suggests that loss of NMI may be a key event allowing increased expression of EMT-inducing transcription factors that drive EMT-dependent malignant progression. Acknowledgement: We acknowledge grant support from the NCI: 1R01CA140472 Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 967. doi:10.1158/1538-7445.AM2011-967