Abstract 2405: Loss of TBK1 induces an epithelial-mesenchymal transition through upregulation of Slug in the breast cancer cell lines

Estrogen receptor alpha (ER alpha) is a key regulator of proliferation and differentiation in mammary epithelium through their well-documented effects on transcription and represents a crucial prognostic indicator and therapeutic target in breast cancer. Here, we show that loss of TBK1 in ER alpha positive breast cancer cells causes an epithelial-mesenchymal transition (EMT). We found that TBK1 is downregulated in ER alpha negative breast tumors by analyzing published microarray data sets, suggesting that TBK1 might regulate ER alpha expression. To investigate this hypothesis, we made the ER alpha positive breast cancer cell lines stably expressing TBK1-specific shRNA. Knockdown of TBK1 decreased E-cadhrein expression (epithelial marker) and increased N-cadherin, vimentin, fibronectin expression (mesenchymal marker). Additionally, loss of TBK1 in ER alpha positive breast cancer cell lines leads to the downregulation of ER alpha expression. Interestingly, ER alpha repression by knockdown of TBK1 induced the upregulation of transcriptional repressor Slug, a master regulator of EMT. Because ER alpha expression is suppressed by loss of TBK1, it is suggested that TBK1 plays a role in the inverse correlation between Slug and ER alpha. Our findings indicate that loss of TBK1 expression is associated in between ER alpha expression status and invasive growth of breast cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2405. doi:1538-7445.AM2012-2405