ESE-1/ELF3 Is a Tumor Suppressor and Molecular Target of Green Tea Compound, EGCG (P05-009-19)

Epithelial Specific ETS-1 (ESE-1), also known as E74-Like Factor 3 (ELF3), belongs to the E26 transformation-specific transcription factor superfamily and is of great interest as a potential target for managing several types of cancer. The objectives of this study are to investigate whether ESE-1/ELF3 is a tumor suppressor and to identify dietary anti-cancer compound to activate ESE-1/ELF3 expression in human colon cancer model. The formation of aberrant crypt foci (ACF) was examined in wild type and ESE-1/ELF3 knockout mice exposed to combination of azoxymethane (AOM) and dextran sulfate sodium (DSS). Stable human colon cancer cell lines expressing ESE-1/ELF3 were established and used for xenograft study and in vitro mechanistic studies. Many bioactive phytochemicals were screened based on the activation of ESE-1/ELF3 expression. ESE-1/ELF3 knockout in mice increased AOM-induced and DSS-promoted formation of ACF. Conversely, overexpression of ESE-1/ELF3 suppressed tumorigenicity in a xenograft mouse study and repressed anchorage-independent growth and migration/invasion in human colon cancer cells. Full length ESE-1/ELF3 localized abundantly in the nucleus, and internal deletion of nuclear localization sequence 2 (NLS2) reduced nuclear ESE-1/ELF3. Three lysine residues (³¹⁸KKK³²⁰) in the NLS2 determine its nuclear localization. We identified epigallocatechin-3-gallate (EGCG) that acts as a transcriptional activator of ESE-1/ELF3 in human colon cancer cells. These findings propose a novel and promising molecular target of dietary anti-cancer compounds for prevention of colon cancer. American Cancer Society.