AUTHOR=Kim Gi-Cheon , Lee Choong-Gu , Verma Ravi , Rudra Dipayan , Kim Taemook , Kang Keunsoo , Nam Jong Hee , Kim Young , Im Sin-Hyeog , Kwon Ho-Keun 

TITLE=ETS1 Suppresses Tumorigenesis of Human Breast Cancer via Trans-Activation of Canonical Tumor Suppressor Genes

JOURNAL=Frontiers in Oncology

VOLUME=10

YEAR=2020

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2020.00642

DOI=10.3389/fonc.2020.00642

ISSN=2234-943X

ABSTRACT=<p><italic>ETS1</italic> has shown dichotomous roles as an oncogene and a tumor suppressor gene in diverse cancers, but its functionality in breast cancer tumorigenesis still remains unclear. We utilized the Cancer Genome Atlas (TCGA) database to analyze comprehensive functions of <italic>ETS1</italic> in human breast cancer (BRCA) patients by investigating its expression patterns and methylation status in relation to clinical prognosis. <italic>ETS1</italic> expression was significantly diminished by hyper-methylation of the <italic>ETS1</italic> promoter region in specimens from BRCA patients compared to a healthy control group. Moreover, <italic>ETS1</italic><sup>high</sup> BRCA patients showed better prognosis and longer survival compared to <italic>ETS1</italic><sup>low</sup> BRCA patients. Consistent with clinical evidence, comparative transcriptome analysis combined with CRISPR/Cas9 or shRNA based perturbation of <italic>ETS1</italic> expression revealed direct as well as indirect mechanisms of <italic>ETS1</italic> that hinder tumorigenesis of BRCA cells. Taken together, our study enlightens a novel function of <italic>ETS1</italic> as a tumor suppressor in breast cancer cells.</p>