Abstract 5161: Identification of epithelial stromal interaction 1 as a novel mediator of breast cancer cell invasion and metastasis downstream of Krüppel-like factor 8.

Abstract

Abstract Epithelial stromal interaction 1 (EPSTI1) is a recently identified novel gene that is highly upregulated in breast cancer cells when co-cultured with the stromal fibroblasts and in invasive breast carcinomas as compared with normal breast biopsies. The regulation and function of EPSTI1 are largely unknown. Our studies showed that EPSTI1 expression is upregulated by Kruppel-like factor 8 (KLF8), a transcriptional factor that is highly over-expressed in breast cancer and critical for cell cycle progression, oncogenic transformation, epithelial to mesenchymal transition (EMT) and metastatic progression of breast cancer, by directly activating EPSTI1 promoter. Also, we demonstrated that EPSTI1 was necessary and sufficient to promote breast cancer cell invasiveness by genetically modifying EPSTI1 expression and Matrigel invasion assays. We also found that EPSTI1 could interact with valosin containing protein (VCP) and subsequently activate NF-kB nuclear function. Finally, our mouse mammary fat pad injection and tail vein injection experiments indicated that ectopic overexpression of EPSTI1 in MCF7 cells could enhance the tumor invasion and metastasis in vivo. These findings suggest that EPSTI1 is a novel target of KLF8 and plays a critical role in the regulation of breast cancer invasion and metastasis. Citation Format: Tianshu Li, Heng Lu, Chao Shen, Satadru Lahiri, Melissa Watson, Debarati Mukherjee, Lin Yu, Jihe Zhao. Identification of epithelial stromal interaction 1 as a novel mediator of breast cancer cell invasion and metastasis downstream of Krüppel-like factor 8. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5161. doi:10.1158/1538-7445.AM2013-5161 Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.