@article{9c1322d643b74690bb648e35cf3b5eb6,
title = "Estrogen receptor beta repurposes EZH2 to suppress oncogenic NFκB/p65 signaling in triple negative breast cancer",
abstract = "Triple Negative Breast Cancer (TNBC) accounts for 15–20% of all breast cancer cases, yet is responsible for a disproportionately high percentage of breast cancer mortalities. Thus, there is an urgent need to identify novel biomarkers and therapeutic targets based on the molecular events driving TNBC pathobiology. Estrogen receptor beta (ERβ) is known to elicit anti-cancer effects in TNBC, however its mechanisms of action remain elusive. Here, we report the expression profiles of ERβ and its association with clinicopathological features and patient outcomes in the largest cohort of TNBC to date. In this cohort, ERβ was expressed in approximately 18% of TNBCs, and expression of ERβ was associated with favorable clinicopathological features, but correlated with different overall survival outcomes according to menopausal status. Mechanistically, ERβ formed a co-repressor complex involving enhancer of zeste homologue 2/polycomb repressive complex 2 (EZH2/PRC2) that functioned to suppress oncogenic NFκB/RELA (p65) activity. Importantly, p65 was shown to be required for formation of this complex and for ERβ-mediated suppression of TNBC. Our findings indicate that ERβ+ tumors exhibit different characteristics compared to ERβ− tumors and demonstrate that ERβ functions as a molecular switch for EZH2, repurposing it for tumor suppressive activities and repression of oncogenic p65 signaling.",
author = "Aspros, {Kirsten G.M.} and Carter, {Jodi M.} and Hoskin, {Tanya L.} and Suman, {Vera J.} and Malayannan Subramaniam and Emch, {Michael J.} and Zhenqing Ye and Zhifu Sun and Sinnwell, {Jason P.} and Thompson, {Kevin J.} and Xiaojia Tang and Rodman, {Esther P.B.} and Xiyin Wang and Nelson, {Adam W.} and Igor Chernukhin and Hamdan, {Feda H.} and Bruinsma, {Elizabeth S.} and Carroll, {Jason S.} and Fernandez-Zapico, {Martin E.} and Johnsen, {Steven A.} and Kalari, {Krishna R.} and Haojie Huang and Leon-Ferre, {Roberto A.} and Couch, {Fergus J.} and Ingle, {James N.} and Goetz, {Matthew P.} and Hawse, {John R.}",
note = "Funding Information: We would like to thank the Mayo Clinic Immunostains Laboratory and Mayo Clinic Pathology Research Core for their time and effort conducting IHC analysis of all patient tumors. We would also like to thank Mayo Clinic, specifically the Department of Biochemistry and Molecular Biology and the Mayo Clinic Graduate School of Biomedical Sciences for their efforts to support this work. Funding of this research was provided by the National Cancer Institute of the National Institutes of Health under award numbers R01CA249116 (JRH) and F31CA228193 (KGMA), the Mayo Clinic Breast Cancer SPORE (PC50CA116201) (JRH, MPG), the Eisenberg Foundation (JRH), the Mayo Foundation (JRH), and the Mayo Clinic Graduate School of Biomedical Sciences (KGMA). Funding Information: We would like to thank the Mayo Clinic Immunostains Laboratory and Mayo Clinic Pathology Research Core for their time and effort conducting IHC analysis of all patient tumors. We would also like to thank Mayo Clinic, specifically the Department of Biochemistry and Molecular Biology and the Mayo Clinic Graduate School of Biomedical Sciences for their efforts to support this work. Funding of this research was provided by the National Cancer Institute of the National Institutes of Health under award numbers R01CA249116 (JRH) and F31CA228193 (KGMA), the Mayo Clinic Breast Cancer SPORE (PC50CA116201) (JRH, MPG), the Eisenberg Foundation (JRH), the Mayo Foundation (JRH), and the Mayo Clinic Graduate School of Biomedical Sciences (KGMA). Publisher Copyright: {\textcopyright} 2022, The Author(s).",
year = "2022",
month = dec,
doi = "10.1038/s41523-022-00387-0",
language = "English (US)",
volume = "8",
journal = "npj Breast Cancer",
issn = "2374-4677",
publisher = "Nature Publishing Group",
number = "1",
}