Identification of epithelial‐specific ETS‐1 (ESE‐1) as a tumor suppressor and molecular target of green tea compound, EGCG

Epithelial specific ETS‐1 (ESE‐1) belongs to the E26 transformation‐specific transcription factor superfamily and is of great interest as a potential target for managing several types of cancer. Despite its clinical significance, the documented effects of ESE‐1 on cancer development and progression are contradictory and its underlying biological mechanism of action remains elusive. The objectives of this study are to investigate whether ESE‐1 is a tumor suppressor and to identify dietary anti‐cancer compound to activate ESE‐1 expression in human colon cancer model. ESE‐1 knockout and xenograft mouse models were used to examine the effect of ESE‐1 in colon tumorigenesis. Stable human colon cancer cell lines were used for in vitro mechanistic studies. ESE‐1 knockout in mice increased azoxymethane (AOM)‐induced and dextran sulfate sodium (DSS)‐promoted formation of aberrant crypt foci (ACF). Conversely, overexpression of ESE‐1 suppressed tumorigenicity in a xenograft mouse study, and repressed anchorage‐independent growth and migration/invasion in human colon cancer cells. Full length ESE‐1 localized abundantly in the nucleus, and internal deletion of nuclear localization sequence 2 (NLS2) reduced nuclear ESE‐1. Three lysine residues ( 318 KKK 320 ) in the NLS2 determine its nuclear localization. We identified epigallocatechin‐3‐gallate (EGCG) that acts as a transcriptional activator of ESE‐1 in human colon cancer cells. These findings propose a novel and promising molecular target of dietary anti‐cancer compounds for prevention of colon cancer.