Open AccessERRα regulates the growth of triple-negative breast cancer cells via S6K1-dependent mechanism
Author(s) -
Adi Y. Berman,
Sukumar Manna,
Naomi Schwartz,
Yardena E Katz,
Yangying Sun,
Catherine A. Behrmann,
Jane Yu,
David R. Plas,
Anya Alayev,
Marina K. Holz
Publication year - 2017
Publication title -
signal transduction and targeted therapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.284
H-Index - 33
eISSN - 2095-9907
pISSN - 2059-3635
DOI - 10.1038/sigtrans.2017.35
Subject(s) - mtorc1 , cancer research , breast cancer , p70 s6 kinase 1 , downregulation and upregulation , cancer , triple negative breast cancer , medicine , biology , pi3k/akt/mtor pathway , signal transduction , endocrinology , oncology , microbiology and biotechnology , gene , genetics
Estrogen-related receptor alpha (ERRα) is an orphan nuclear factor that is a master regulator of cellular energy metabolism. ERRα is overexpressed in a variety of tumors, including ovarian, prostate, colorectal, cervical and breast, and is associated with a more aggressive tumor and a worse outcome. In breast cancer, specifically, high ERRα expression is associated with an increased rate of recurrence and a poor prognosis. Because of the common functions of ERRα and the mTORC1/S6K1 signaling pathway in regulation of cellular metabolism and breast cancer pathogenesis, we focused on investigating the biochemical relationship between ERRα and S6K1. We found that ERRα negatively regulates S6K1 expression by directly binding to its promoter. Downregulation of ERRα expression sensitized ERα-negative breast cancer cells to mTORC1/S6K1 inhibitors. Therefore, our results show that combinatorial inhibition of ERRα and mTORC1/S6K1 may have clinical utility in treatment of triple-negative breast cancer, and warrants further investigation.